[ CAS No. 147-71-7 ] {[proInfo.proName]}

Name: 147-71-7|(2S,3S)-2,3-Dihydroxysuccinic acid|98%
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Quality Control of [ 147-71-7 ]

COA NMR CNMR HPLC LC-MS

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SDS Specification

Alternatived Products of [ 147-71-7 ]

Product Details of [ 147-71-7 ]

CAS No. :	147-71-7	MDL No. :	MFCD00004238
Formula :	C₄H₆O₆	Boiling Point :	-
Linear Structure Formula :	-	InChI Key :	FEWJPZIEWOKRBE-LWMBPPNESA-N
M.W :	150.09	Pubchem ID :	439655
Synonyms :		Chemical Name :	(2S,3S)-2,3-Dihydroxysuccinic acid

Calculated chemistry of [ 147-71-7 ]

Physicochemical Properties

Num. heavy atoms :	10
Num. arom. heavy atoms :	0
Fraction Csp3 :	0.5
Num. rotatable bonds :	3
Num. H-bond acceptors :	6.0
Num. H-bond donors :	4.0
Molar Refractivity :	27.21
TPSA :	115.06 Å²

Pharmacokinetics

GI absorption :	Low
BBB permeant :	No
P-gp substrate :	No
CYP1A2 inhibitor :	No
CYP2C19 inhibitor :	No
CYP2C9 inhibitor :	No
CYP2D6 inhibitor :	No
CYP3A4 inhibitor :	No
Log Kp (skin permeation) :	-8.55 cm/s

Lipophilicity

Log Po/w (iLOGP) :	-0.82
Log Po/w (XLOGP3) :	-1.88
Log Po/w (WLOGP) :	-2.12
Log Po/w (MLOGP) :	-2.18
Log Po/w (SILICOS-IT) :	-1.88
Consensus Log Po/w :	-1.78

Druglikeness

Lipinski :	0.0
Ghose :	None
Veber :	0.0
Egan :	0.0
Muegge :	2.0
Bioavailability Score :	0.56

Water Solubility

Log S (ESOL) :	0.61
Solubility :	614.0 mg/ml ; 4.09 mol/l
Class :	Highly soluble
Log S (Ali) :	-0.02
Solubility :	144.0 mg/ml ; 0.963 mol/l
Class :	Very soluble
Log S (SILICOS-IT) :	2.44
Solubility :	41700.0 mg/ml ; 278.0 mol/l
Class :	Soluble

Medicinal Chemistry

PAINS :	0.0 alert
Brenk :	0.0 alert
Leadlikeness :	1.0
Synthetic accessibility :	2.57

Safety of [ 147-71-7 ]

Signal Word:	Warning	Class:	N/A
Precautionary Statements:	P261-P305+P351+P338	UN#:	N/A
Hazard Statements:	H315-H319-H335	Packing Group:	N/A
GHS Pictogram:

Application In Synthesis of [ 147-71-7 ]

* All experimental methods are cited from the reference, please refer to the original source for details. We do not guarantee the accuracy of the content in the reference.

Upstream synthesis route of [ 147-71-7 ]
Downstream synthetic route of [ 147-71-7 ]

[ 147-71-7 ] Synthesis Path-Upstream 1~9

1
[ 67-56-1 ]
[ 147-71-7 ]
[ 13171-64-7 ]

Reference： [1] Chirality, 2018, vol. 30, # 4, p. 342 - 350
[2] Journal of Fluorine Chemistry, 1980, vol. 15, p. 191 - 200
[3] Journal of the American Chemical Society, 1978, vol. 100, # 15, p. 4865 - 4872
[4] Journal of Organic Chemistry, 2004, vol. 69, # 16, p. 5433 - 5438
[5] Organic letters, 2001, vol. 3, # 15, p. 2349 - 2351
[6] Tetrahedron Letters, 2013, vol. 54, # 42, p. 5674 - 5676
[7] Tetrahedron, 2015, vol. 71, # 33, p. 5362 - 5370
[8] Organic Letters, 2015, vol. 17, # 18, p. 4596 - 4599

2
[ 147-71-7 ]
[ 149-73-5 ]
[ 13171-64-7 ]

Reference： [1] Monatshefte fur Chemie, 2014, vol. 145, # 2, p. 305 - 309

3
[ 64-17-5 ]
[ 147-71-7 ]
[ 13811-71-7 ]

Yield	Reaction Conditions	Operation in experiment
97%	Stage #1: With hydrogenchloride In water at 70 - 80℃; Stage #2: at 30 - 40℃;	[Refining procedures of 1st]: in a thermometer is arranged, is put in a flask of agitator D-tartaric acid (malic acid 0.20percent, fumaric acid 0.07percent) 60.0g and ethanol 36.0g, in 10 °C lower stirring 2 hours later, through the filter recovery D-tartaric acid 48.1 g. [Process 1st]: the [of the refining procedures of 1st] D-tartaric acid in dry, add ethanol 28.8g, by adding 35percent hydrochloric acid 1.9g, in 80 °C to enable its reaction under. Next, in the 70 °C the following concentrate, before adding the same quantity of ethanol and 35percent hydrochloric acid, to concentrate similarly after the reaction. Recognizing the moisture 0.1 weight percent, to obtain 1st esterification reaction liquid. [Process 2nd]: 1st the obtained in the esterification reaction solution before the addition of ethanol to stir the same, then adding thionyl chloride 11.4g, in 30-40 °C to enable its reaction under. Concentration is carried out, to obtain 2nd esterification reaction liquid. [Process 3rd]: 2nd the esterification reaction solution of sodium bicarbonate and in the rear, to filter the obtained filtrate is concentrated (D-tartaric acid diethyl ester which yield 97percent). Finally, under reduced pressure, through the thin film distillation (heat medium temperature 145 °C) separating D-diethyl tartrate of the optical purity is 99.8percent ee, malic acid diethyl ester and fumaric acid diethyl ester content is less than 0.01percent. Furthermore, sulfurous acid diethyl ester and tartaric acid monoethyl the content is less than 0.01percent, and 0.02percent.

Reference： [1] Tetrahedron, 2007, vol. 63, # 27, p. 6346 - 6357
[2] Tetrahedron Asymmetry, 2011, vol. 22, # 3, p. 257 - 263
[3] RSC Advances, 2014, vol. 4, # 90, p. 48827 - 48835
[4] RSC Advances, 2013, vol. 3, # 43, p. 20298 - 20307
[5] Patent: CN104003883, 2016, B, . Location in patent: Paragraph 0165-0170
[6] Collection of Czechoslovak Chemical Communications, 1982, vol. 47, # 1, p. 173 - 189
[7] Journal of the Chemical Society, Perkin Transactions 1: Organic and Bio-Organic Chemistry (1972-1999), 1993, # 7, p. 805 - 812
[8] Tetrahedron Asymmetry, 2001, vol. 12, # 22, p. 3081 - 3088
[9] Tetrahedron, 1984, vol. 40, # 22, p. 4617 - 4623
[10] Tetrahedron Letters, 2009, vol. 50, # 32, p. 4592 - 4594

4
[ 147-71-7 ]
[ 98-88-4 ]
[ 17026-42-5 ]

Reference： [1] Journal of Chemical Research, Miniprint, 1984, # 5, p. 1518 - 1530

5
[ 147-71-7 ]
[ 6537-80-0 ]

Reference： [1] Tetrahedron, 1958, vol. 4, p. 43,44, 45

6
[ 147-71-7 ]
[ 100-46-9 ]
[ 163439-82-5 ]

Reference： [1] Collection of Czechoslovak Chemical Communications, 2012, vol. 77, # 3, p. 224 - 233

7
[ 147-71-7 ]
[ 104617-86-9 ]
[ 104632-28-2 ]
[ 104632-26-0 ]

Reference： [1] Patent: WO2010/22140, 2010, A1, . Location in patent: Page/Page column 100-101

8
[ 147-71-7 ]
[ 190791-29-8 ]

Yield	Reaction Conditions	Operation in experiment
50.3%	for 0.0833333 h; Reflux	The racemic base 2b, prepared in Example 3, optionally purified as described in Example 4, 5 or 6, in the quantity of 17.2 g is dissolved in 172 ml of warm wine spirit. A solution of 6.24 g of D-tartaric acid in 62 ml of wine spirit is added to this solution and the resulting solution is carefully heated to slight reflux for 5 minutes. During spontaneous cooling the required lasofoxifene D-tartrate precipitates in the yield of 11.8 g, i.e. 50.3percent.

Reference： [1] Patent: US2010/256394, 2010, A1, . Location in patent: Page/Page column 8

9
[ 147-71-7 ]
[ 180916-16-9 ]
[ 190791-29-8 ]

Yield	Reaction Conditions	Operation in experiment
50%	for 0.0833333 h; Reflux	Purified lasofoxifene (2 g) from step d was dissolved in 20 mL of 95ethanol, and mixed together with 0.78 g D-tartaric acid, which is dissolved in 7.8 mL of 95ethanol. The mixed solution was carefully heated to slight reflux for 5 minutes, and then cooled to room temperature. About 1.4 g precipitation of lasofoxifene D-tartrate salt was obtained (Yield 50) .[0163]Lasofoxifene D-tartrate was dissolved in DMSO-d₆(50 mg/mL) for NMR analysis.¹H NMR (600 MHz, DMSO-d₆) δ 1.711.85 (m, 5H) , 2.08 (s, 1H) , 2.902.99 (m, 6H) , 3.17 (br, 2H) , 3.295 (m, 1H) , 4.024.06 (m, 4H) , 4.17 (d, J 3.6 Hz, lH) 4.43 (br, 2H) , 6.6 (m, 5H) , 6.81 (d, J 6.4 Hz, 2H) , 7.11 (s, 1H) , 7.13 (s, 2H) .¹³C NMR (150 MHz, DMSO-d₆) δ 174.26, 155.74, 155.36, 144.12, 137.08, 135.37, 131.09, 130.97, 130.04, 127.83, 127.61, 125.87, 114.35, 113.58, 112.91, 71.90, 64.07, 53.59, 53.100, 49.40, 44.41, 29.244, 22.56, 22.41.

Reference： [1] Patent: WO2018/129645, 2018, A1, . Location in patent: Paragraph 0140; 0146-0147

[ 147-71-7 ] Synthesis Path-Downstream 1~88

1
[ 74-90-8 ]
[ 453-17-8 ]
[ 147-71-7 ]

Reference： [1]Chemische Berichte,1917,vol. 50,p. 456
Chemische Berichte,1914,vol. 47,p. 3357

2
[ 147-71-7 ]
[ 6537-80-0 ]

Reference： [1]Tetrahedron,1958,vol. 4,p. 43,44, 45

3
[ 63-42-3 ]
[ 147-71-7 ]

Reference： [1]Chemische Berichte,1908,vol. 41,p. 2650

4
[ 67-56-1 ]
[ 147-71-7 ]
[ 13171-64-7 ]

Yield	Reaction Conditions	Operation in experiment
	With thionyl chloride; at 20℃; for 12h;	General procedure: Compounds 1-6 and 10-11 (3.0 mg each) were, respectively, dissolved in 100 muL methanol and added to 100 muL 10% K2CO3 (methanol/water 2: 1, v/v). After hydrolysis at 60C for 2 h, the reaction mixtures were blow-dried, then acidified by 0.1 M HCl (500 muL) and extracted with EtOAc (500 muL×3). The aqueous layers were blow-dried and dissolved in methanol (200 muL). A drop of SOCl2 was added to the solution to catalyze the esterification (room temperature, 12 h). After evaporation, the mixed methyl esters of 4-hydroxytiglic acid and malic acid (or tartaric acid) were dissolved in dry pyridine (100 muL) and reacted with (S)-MTPA chloride (2 muL) overnight to obtain the final products. The corresponding authentic (R)-MTPA esters were also prepared from the commercial D-malic acid, L-malic acid, D-tartaric acid and L-tartaric acid. The 1H NMR data of the authentic (R)-MTPA esters of dimethyl malates were in accord with the reported.8

Reference： [1]Chirality,2018,vol. 30,p. 342 - 350
[2]Journal of Fluorine Chemistry,1980,vol. 15,p. 191 - 200
[3]Journal of the American Chemical Society,1978,vol. 100,p. 4865 - 4872
[4]Journal of Organic Chemistry,2004,vol. 69,p. 5433 - 5438
[5]Organic letters,2001,vol. 3,p. 2349 - 2351
[6]Tetrahedron Letters,2013,vol. 54,p. 5674 - 5676
[7]Tetrahedron,2015,vol. 71,p. 5362 - 5370
[8]Organic Letters,2015,vol. 17,p. 4596 - 4599

5
[ 64-17-5 ]
[ 147-71-7 ]
[ 13811-71-7 ]

Yield	Reaction Conditions	Operation in experiment
100%	With thionyl chloride at 20℃;
100%	With thionyl chloride at 20℃;
99.6%	With hydrogenchloride In chloroform; water for 60h; Reflux; enantioselective reaction;

98%	With sulfuric acid Reflux;
97%	Stage #1: ethanol; D-tartaric acid With hydrogenchloride In water at 70 - 80℃; Stage #2: With thionyl chloride at 30 - 40℃;	5 [Refining procedures of 1st]: in a thermometer is arranged, is put in a flask of agitator D-tartaric acid (malic acid 0.20%, fumaric acid 0.07%) 60.0g and ethanol 36.0g, in 10 °C lower stirring 2 hours later, through the filter recovery D-tartaric acid 48.1 g. [Process 1st]: the [of the refining procedures of 1st] D-tartaric acid in dry, add ethanol 28.8g, by adding 35% hydrochloric acid 1.9g, in 80 °C to enable its reaction under. Next, in the 70 °C the following concentrate, before adding the same quantity of ethanol and 35% hydrochloric acid, to concentrate similarly after the reaction. Recognizing the moisture 0.1 weight %, to obtain 1st esterification reaction liquid. [Process 2nd]: 1st the obtained in the esterification reaction solution before the addition of ethanol to stir the same, then adding thionyl chloride 11.4g, in 30-40 °C to enable its reaction under. Concentration is carried out, to obtain 2nd esterification reaction liquid. [Process 3rd]: 2nd the esterification reaction solution of sodium bicarbonate and in the rear, to filter the obtained filtrate is concentrated (D-tartaric acid diethyl ester which yield 97%). Finally, under reduced pressure, through the thin film distillation (heat medium temperature 145 °C) separating D-diethyl tartrate of the optical purity is 99.8% ee, malic acid diethyl ester and fumaric acid diethyl ester content is less than 0.01%. Furthermore, sulfurous acid diethyl ester and tartaric acid monoethyl the content is less than 0.01%, and 0.02%.
91%	With sulfuric acid In benzene Heating;
91%	With Dowex 50W-X₈ (H+) In benzene for 24h; Heating;
91%	With acid
87.6%	With thionyl chloride at 20℃;	1.2.1. diethyl (2S,3S)-2,3-dihydroxysuccinate e To a solution of L-tartaric acid (15.02 g, 100.1 mmol) in EtOH (150 mL), SOCl2 (16.0 mL, 220.3 mmol) was added dropwise. The mixture was stirred at room temperature overnight. The solvent was evaporated in vacuum and CH2Cl2 (30 mL) was added to the mixture. The resulting mixture was washed with saturated aqueous NaHCO3 (30 mL) and the aqueous layer was extracted with CH2Cl2. The combined organic extracts were washed with brine (2×30 mL), dried over anhydrous Na2SO4, filtered, and concentrated in vacuum, to obtain the desired product e (18.08 g) as yellow oil liquid, yield: 87.6%. 1H NMR (600 MHz, CDCl3) δ 4.47 (s, 2H, CH), 4.28-4.22 (m, 4H, CH3CH2O), 3.18 (s, 2H, OH), 1.26 (t, J = 7.2 Hz, 6H, CH3CH2O).
82%	With sulfuric acid
53%	With thionyl chloride at 0 - 20℃; Inert atmosphere;
	With hydrogenchloride In water for 8h; Reflux;

Reference： [1]Zhou, Xiang; Liu, Wen-Jun; Ye, Jian-Liang; Huang, Pei-Qiang [Tetrahedron, 2007, vol. 63, # 27, p. 6346 - 6357]
[2]Location in patent: scheme or table Zheng, Jin-Li; Liu, Hui; Zhang, Yu-Feng; Zhao, Wei; Tong, Jin-Shuan; Ruan, Yuan-Ping; Huang, Pei-Qiang [Tetrahedron Asymmetry, 2011, vol. 22, # 3, p. 257 - 263]
[3]Alavi, Sohaila; Hosseini-Monfared, Hassan; Aleshkevych, Pavlo [RSC Advances, 2014, vol. 4, # 90, p. 48827 - 48835]
[4]Zeng, Jing; Zhang, Qian; Zhang, Hong-Kui; Chen, Anqi [RSC Advances, 2013, vol. 3, # 43, p. 20298 - 20307]
[5]Current Patent Assignee: TORAY INDUSTRIES INC - CN104003883, 2016, B Location in patent: Paragraph 0165-0170
[6]HOLY, Antonin [Collection of Czechoslovak Chemical Communications, 1982, vol. 47, # 1, p. 173 - 189]
[7]Crout, David H. G.; Gaudet, S. B.; Hallinan, Keith O. [Journal of the Chemical Society. Perkin transactions I, 1993, # 7, p. 805 - 812]
[8]Jiao, Peng; Xu, Jiaxi; Zhang, Qihan; Choi, Michael C.K.; Chan, Albert S.C. [Tetrahedron Asymmetry, 2001, vol. 12, # 22, p. 3081 - 3088]
[9]Li, Bing; Wang, Kaiyuan; Zhang, Rui; Li, Baihui; Shen, Yangli; Ji, Qinggang [European Journal of Medicinal Chemistry, 2019, vol. 182]
[10]Tamoto; Sugimori; Terashima [Tetrahedron, 1984, vol. 40, # 22, p. 4617 - 4623]
[11]Wang, Pei; Ma, Guo-Rong; Yu, Sheng-Li; Da, Chao-Shan [Chirality, 2019, vol. 31, # 1, p. 79 - 86]
[12]Liu, Jian-Hua; Long, Ya-Qiu [Tetrahedron Letters, 2009, vol. 50, # 32, p. 4592 - 4594]

6
[ 147-71-7 ]
[ 100-51-6 ]
[ 4136-22-5 ]

Reference： [1]Journal of the American Chemical Society,1996,vol. 118,p. 4550 - 4559
[2]Tetrahedron,2003,vol. 59,p. 3899 - 3915
[3]Journal of Pharmaceutical Sciences,1965,vol. 54,p. 1269 - 1273

7
[ 67-56-1 ]
[ 147-71-7 ]
[ 77-76-9 ]
(+)-dimethyl-2,3-O-isopropylidene-D-tartrate [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
80%	Stage #1: methanol; D-tartaric acid; 2,2-dimethoxy-propane With toluene-4-sulfonic acid Heating; Stage #2: In cyclohexane Heating;
78%	In cyclohexane for 1.5h; Heating / reflux;	1; 2.1 A solution of L-tartaric acid (80g, 533mol), p-toluenesulfonic acid (0.32g, 1.86mmoi)and 2,2-dimethoxypropane (127g, 1.2mol) was refluxed gently with stirring for 1.5hours. Cyclohexane and further 2,2-diemthoxypropane (63.7ml, 0.63mol) was addedand azeotropes slowly removed form the head of a vigreaux column. Afterapproximately three days the solution was allowed to cool to room temperature andanhydrous potassium carbonate added to neutralize the catalyst. The solution was thenfiltered and the solvent removed in-vacuo. The crude product was then distilled at highvacuum to give dimethyl 2,3-O-isopropylidene-L-tartarate (90g, 412mmol 78%) as ayellow oil. 1H NMR (CDC13): 5 4.85 (s, 2H), 3.86 (s, 6H), 1.53 (s, 6H); 13C NMR(CDC13): 5 172.16,114.13, 72.25, 53.40, 26.55; LRCDVIS: 218.9 (M+l).
77%	With toluene-4-sulfonic acid In 1,4-dioxane Inert atmosphere;

	With toluene-4-sulfonic acid 1.) reflux, 1.5 h, 2.) cyclohexane, reflux, 42 h; Yield given; Multistep reaction;
	With toluene-4-sulfonic acid In benzene Heating;
	With toluene-4-sulfonic acid at 20℃; for 48h; Inert atmosphere; Reflux;

Reference： [1]Li, Baohua; Yang, Xuemei; Yang, Kai; Fu, Enqin [Synthetic Communications, 2005, vol. 35, # 19, p. 2603 - 2608]
[2]Current Patent Assignee: POLYCHIP PHARMACEUTICALS; UNIVERSITY OF SYDNEY - WO2006/43, 2006, A1 Location in patent: Page/Page column 11-12
[3]Miyazawa, Yuki; Sugimoto, Makoto; Tanaka-Oda, Ayumi; Makabe, Hidefumi [Tetrahedron Letters, 2019, vol. 60, # 36]
[4]Agganval, Varinder K.; Masters, Susannah J.; Adams, Harry; Spey, Sharon E.; Brown, George R.; Foubister, Alan J. [Journal of the Chemical Society. Perkin transactions I, 1999, # 2, p. 155 - 162]
[5]Kim; Bae; So; Yoo; Chang; Lee; Kang [Organic letters, 2001, vol. 3, # 15, p. 2349 - 2351]
[6]Lo, Hong-Jay; Chang, Yuan-Kang; Yan, Tu-Hsin [Organic Letters, 2012, vol. 14, # 23, p. 5896 - 5899]

8
[ 147-71-7 ]
[ 67198-21-4 ]
(R,R)-1-ammonium-2-(dimethylammonium)cyclohexane mono-L-tartrate [ No CAS ]

Reference： [1]Tetrahedron,2001,vol. 57,p. 1765 - 1769

9
[ 147-71-7 ]
[ 77-76-9 ]
(+)-dimethyl-2,3-O-isopropylidene-D-tartrate [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
100%	With toluene-4-sulfonic acid In methanol; cyclohexane at 52 - 54℃;
91%	With toluene-4-sulfonic acid Heating;
88%	With toluene-4-sulfonic acid In methanol; cyclohexane at 102℃; for 0.25h; Reflux;

84%	With toluene-4-sulfonic acid In methanol at 20℃; Inert atmosphere;
83%	With toluene-4-sulfonic acid In methanol at 25℃; Reflux; Inert atmosphere;
81%	With toluene-4-sulfonic acid In methanol; cyclohexane at 70℃; for 7h; Inert atmosphere;	Dimethyl 2,3-O-isopropylidene-D-tartrate (S1) To a suspension of D-tartaric acid (25 g, 168 mmol) and methanol (10 mL) was added 2,2-dimethoxypropane (47.5 mL) and p-TSA (ca. 100 mg). The reaction was heated to 70 °C and stirred at this temperature until a dark red color was obtained (~1 h). Additional 2,2-dimethoxypropane (25 mL) and cyclohexane (113 mL) were added. The flask was fitted with a Vigreux column and shortpath distillation head. The mixture was heated and the acetone-cyclohexane and methanol-cyclohexane azeotrope was slowly removed over 6 h (ca. 150 mL). The mixture was cooled to room temperature and potassium carbonate (250 mg) was added. The reaction was stirred until the dark red color abated. Volatiles were removed in vacuo and the product was purified by vacuum distillation (0.5 mm Hg, 94-110°C) to yield S1 (29.8 g, 81%) as a clear oil. The spectral data matched reported values.
	With toluene-4-sulfonic acid In methanol; cyclohexane

Reference： [1]Albizati, Kim F.; Babu, Srinivasan; Birchler, Angela; Busse, Juliette K.; Fugett, Michelle; Grubbs, Alan; Haddach, Aubrey; Pagan, Miguel; Potts, Barbara; Remarchuk, Travis; Rieger, Dale; Rodriguez, Rick; Shanley, Jim; Szendroi, Robert; Tibbetts, Tony; Whitten, Kathleen; Borer, Bennett C. [Tetrahedron Letters, 2001, vol. 42, # 37, p. 6481 - 6485]
[2]Davoli, Paolo; Spaggiari, Alberto; Castagnetti, Luca; Prati, Fabio [Organic and Biomolecular Chemistry, 2004, vol. 2, # 1, p. 38 - 47]
[3]Raghavan, Sadagopan; Nyalata, Satyanarayana [Journal of Organic Chemistry, 2016, vol. 81, # 22, p. 10698 - 10706]
[4]Location in patent: scheme or table Zang, Qin; Gulab, Shivali; Stocker, Bridget L.; Baars, Sylvia; Hoberg, John O. [European Journal of Organic Chemistry, 2011, # 23, p. 4465 - 4471]
[5]Location in patent: experimental part Lo, Hong-Jay; Chen, Cheng-Yih; Zheng, Wei-Lin; Yeh, Shang-Ming; Yan, Tu-Hsin [European Journal of Organic Chemistry, 2012, # 14, p. 2780 - 2785]
[6]Davis, Robert W.; Allweil, Alexander; Tian, Jianhua; Brash, Alan R.; Sulikowski, Gary A. [Tetrahedron Letters, 2018, vol. 59, # 52, p. 4571 - 4573]
[7]Location in patent: scheme or table Nishiyama, Taihei; Kusumoto, Yoshifumi; Okumura, Ken; Hara, Kanako; Kusaba, Shohei; Hirata, Keiko; Kamiya, Yukihiro; Isobe, Minoru; Nakano, Keiji; Kotsuki, Hiyoshizo; Ichikawa, Yoshiyasu [Chemistry - A European Journal, 2010, vol. 16, # 2, p. 600 - 610]

10
[ 508233-74-7 ]
[ 147-71-7 ]
Vortioxetine D-Tartrate [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
68%	In acetone at 20℃; for 0.5h;	11a Example 11a; Preparation of D-(-)-tartrate of compound I; 11.1 ml of a 0.30 M solution of l-[2-(2,4-Dimethylphenylsulfanyl)-phenyl]piperazine in acetone was treated with 0.5 gram D-(-)-tartaric acid dissolved in 5 ml acetone. The mixture was stirred at room temperature for 30 minutes during which precipitation took place. Filtration and washing first with 5 ml acetone and then 3 ml diethyl ether produced the product as a white solid that was dried in vacuum (50 0C) over night. 1- [2-(2,4-Dimethylphenylsulfanyl)-phenyl]piperazine D-(-)-tartaric acid was isolated in 1.0 gram (68 %). NMR complies with structure. Elemental analysis: 58.90%C, 6.26%N, 6.35%H (Theory for a 1:1 salt: 58.91%C, 6.25%N, 6.29%H); Example l ib; Characterisation of the D-(-)-tartrate of compound I; The D-(+)-tartrate, as prepared in example l la, is crystalline (XRPD) - see Figure 14.It has a melting point of ~175°C. The solubility in water is -0.4 mg/ml.
68%	In acetone at 20℃; for 0.5h;	10a Example IQa Preparation of D-(-)-tartrate of compound I11.1 ml of a 0.30 M solution of l-[2-(2,4-Dimethylphenylsulfanyl)-phenyl]piperazine in acetone was treated with 0.5 gram D-(-)-tartaric acid dissolved in 5 ml acetone. The mixture was stirred at room temperature for 30 minutes during which precipitation took place. Filtration and washing first with 5 ml acetone and then 3 ml diethyl ether produced the product as a white solid that was dried in vacuum (50 0C) over night. 1- [2-(2,4-Dimethylphenylsulfanyl)-phenyl]piperazine D-(-)-tartaric acid was isolated in 1.0 gram (68 %). NMR complies with structure. Elemental analysis: 58.90%C, 6.26%N, 6.35%H (Theory for a 1:1 salt: 58.91%C, 6.25%N, 6.29%H)

Reference： [1]Current Patent Assignee: H. LUNDBECK A/S - WO2007/144005, 2007, A1 Location in patent: Page/Page column 36
[2]Current Patent Assignee: H. LUNDBECK A/S - WO2008/113359, 2008, A2 Location in patent: Page/Page column 22

11
[ 147-71-7 ]
[ 88150-42-9 ]
[ 67-68-5 ]
S-(-)-amlodipine-hemi-D-tartrate mono-dimethylsulfoxide solvate [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
	at 20℃; for 12h;Resolution of racemate;Purification / work up;	Example; Preparation 1: Preparation of S-(-)-amlodipine-hemi-D-tartrate-mono- dimethyl sulfoxide solvate; 1.5 kg of (R/S)-amlodipine was dissolved in 7.5 I of dimethyl sulfoxide, to which a solution of 275.3 g of D-(-)-tartaric acid in 7.5 Z of dimethyl sulfoxide was slowly added dropwise with stirring at room temperature. The resulting slurry was further stirred at room temperature for 12 hours, and the precipitated solid was filtered, washed with 6.0 Z of <n="9"/>dimethyl sulfoxide and 6.0 I of acetone, and dried under a warm air flow at 40 C overnight, to obtain 771 g (yield: 37.4%) of the title compound in the form of a white solid.Optical purity: 98.2% ee

Reference： [1]Patent: WO2008/10659,2008,A1 .Location in patent: Page/Page column 6-7

12
[ 147-71-7 ]
[ 22990-19-8 ]
[ 869884-00-4 ]

Yield	Reaction Conditions	Operation in experiment
89%	In water; ethyl acetate; at 25 - 60℃; for 1.5h;Product distribution / selectivity;	A round bottom flask was loaded with IQL (50 g), EtOAc (350 ml), and water (150 ml). The mixture was heated to 60 C. for dissolution. Then D-tartaric acid (36 g) was added, and the solution was cooled to 25 C. The product was isolated after 1.5 hours by vacuum filtration, washed with EtOAc (2×50 ml), dried in vacuum oven at 50 C. overnight to obtain (S)-IQL tartrate (37.25 g, 89% yield, 94.5% enantiomeric purity).
75.5 - 99.8%	In water; isopropyl alcohol; at 5 - 60℃; for 2.5 - 15h;Product distribution / selectivity;	A round bottom flask was loaded with IQL (50 g), IPA (350 ml), and water (150 ml). The mixture was heated to 60 C. for dissolution. Then D-tartaric acid (36 g) was added, and the solution was cooled to 25 C. The product was isolated after 2.5 hours by vacuum filtration, washed with IPA (2×50 ml), dried in a vacuum oven at 50 C. over the weekend to obtain (S)-IQL tartrate (33.5 g, 80% yield, 100% enantiomeric purity). ; A round bottom flask was loaded ask was loaded with IQL (10 g), IPA, and water. The mixture was heated to 60 C. for dissolution. Then D-tartaric acid was added, and the solution was cooled and stirred. Where applicable, seeding was performed during the cooling step. The product was isolated by vacuum filtration, washed with a mixture of water and IPA, and dried in vacuum oven at 50 C. over the TABLE 1 Tartaric Stirring acid Acid time (molar IPAH2O addition after Cooling equiv. (ml/g (ml/g temp. cooling temp. Enantiomeric Yield to IQL) of IQL) of IQL) ( C.) Seeding (hrs) ( C.) Purity (%) 1 7 3 60 - 2.5 RT 98.4 83.5 1 6 3 60 - 2.5 RT 98.6 81.4 1 7 2 60 - 2.5 RT 98.8 87.1 1 7 4 60 - 2.5 RT 97.7 75.5 1 5.6 2.4 60 - 2.5 RT 98.2 85.0 1 8.4 3.6 60 - 2.5 RT 99.8 77.1 1 7 3 40 - 2.5 RT 98.1 80.0 1 7 3 25 - 2.5 RT 97.6 79.0 1 7 3 60 + 2.5 RT 98.7 77.9 1 7 3 60 - 5 RT 98.7 79.2 1 7 3 60 - 15 RT 89.9 85.4 1 7 3 60 - 2.5 15 C. 99.6 91.8 1 7 3 60 - 2.5 5 C. 99.5 92.0 weekend to obtain (S)-IQL tartrate. The experiments and results are summarized in Table 1.
43.7%	In water; isopropyl alcohol; at 70℃; for 0.5h;	1. 4 will be 43. 63g (0.208mol) 1.3 Phenyl-1,2,3,4-dihydroisoquinoline obtained in the above step (1) was dissolved 305 ml of isopropanol and 130 ml of water,Heated to 70 C, the raw materials completely dissolved,Then, 31. 28 g (0.208 m?) of D-tartaric acid was added,And the reaction temperature 30min, to tartaric acid completely dissolved, stop heating and cooling to room temperature, continue stirring for 3h, a white crystal precipitation, filtration, and washing with isopropanol, the white solid drying at 50 C,(S) -l-phenyl-1,2,3,4-tetrahydroisoquinoline tartrate 32. 75 g, yield 43.7%.

43.7%

In water; isopropyl alcohol; at 70℃; for 0.5h;

43.63 g (0.208 mol) of 3.3[22990-19-8]1-phenyl-1,2,3,4-dihydroisoquinoline is soluble305 ml of isopropanol and 130 ml of water, heated to 70 C,Completely dissolve the raw materials,Then added 31.28 g (0.208 mol) of D-tartaric acid,And reacted at this temperature for 30 min,Completely dissolve the tartaric acid, stop heating, and cool to room temperature, continue stirring for 3 h.White crystals were precipitated, suction filtered, and washed with isopropyl alcohol.The resulting white solid was dried at 50 C overnight.get(S)-[22990-19-8]1-phenyl-1,2,3,4-tetrahydroisoquinoline tartrate32.67 g, yield 43.7%.

Reference： [1]Patent: US2008/91023,2008,A1 .Location in patent: Page/Page column 5
[2]Patent: US2008/91023,2008,A1 .Location in patent: Page/Page column 4-5
[3]Patent: CN103159677,2016,B .Location in patent: Paragraph 0065; 0069
[4]Patent: CN109438348,2019,A .Location in patent: Paragraph 0026
[5]Journal of the American Chemical Society,2013,vol. 135,p. 10863 - 10869

13
D-sodium hydrogen tartrate [ No CAS ]
[ 147-71-7 ]

Yield	Reaction Conditions	Operation in experiment
83%	With sulfuric acid In ethanol at 20℃; for 0.75h;	4 EXAMPLE 4 Preparation of Crystalline D-tartaric Acid from Recovered D-sodium Hydrogen Tartrate in Ethanol A slurry of recovered D-sodium hydrogen tartrate (50.5 g, 0.293 mol) in ethanol is treated with concentrated sulfuric acid (15.0 g, 0.147 mol) at room temperature, stirred for 45 minutes and filtered to remove inorganic salts. The filtrate is concentrated in vacuo to afford a concentrated slurry of D-tartaric acid in ethanol. The slurry is diluted with toluene and filtered. The filtercake is washed with toluene and dried to afford D-tartaric acid as a crystalline solid, 37.3 g, (83% yield) 97.7% purity 100% optical purity as determined by HPLC analysis.
82%	With sulfuric acid In methanol at 20℃; for 1h;	3 EXAMPLE 3 Preparation of (R)-2-Amino-2,3-dimethylbutyronitrile (2S,3S)-tartrate from Recovered D-sodium Hydrogen Tartrate A slurry of recovered D-sodium hydrogen tartrate (20.6 g, 0.119 mol) in methanol is treated with concentrated sulfuric acid (6.1 g, 0.059 mol) at room temperature, stirred for one hour and filtered to remove inorganic salts. A portion of the filtrate is concentrated in vacuo to give a solution of recovered D-tartaric acid (13.6 g, 0.090 mol, 82%) in methanol.

Reference： [1]Current Patent Assignee: BASF SE - US6346649, 2002, B1 Location in patent: Page column 7
[2]Current Patent Assignee: BASF SE - US6346649, 2002, B1 Location in patent: Page column 6

14
[ 147-71-7 ]
(2-methyl-5-piperidin-3-ylphenoxy)acetic acid ethyl ester D-tartaric acid salt [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
55%	Stage #1: 3-(3-ethoxycarbonylmethoxy-4-methylphenyl)piperidine-1-carboxylic acid benzyl ester With hydrogen In ethanol; water for 2h; Stage #2: D-tartaric acid In ethanol at 20℃; for 24h;	12-2 Example 12-2; (R)- (2-METHYL-5- {1- [4-METHYL-2- (4-TRIFLUOROMETHYL-PHENYL)-THIAZOLE-5-CARBONYL]- piperidin-3-yl}-phenoxy)-acetic acid To a solution of 3- (3-hydroxy-4-methyl-phenyl)-piperidine-1-carboxylic acid benzyl ester (Example 11-2; 2.34g, 7.19 mmol) in 15 mL DIMETHYLFORMAMIDE was added cesium carbonate (4.69g, 14.38 mmol) and ethyl bromoacetate (1.60 mL, 14.38 MMOL). The mixture was heated to 60°C under N2 with stirring for 3 h and cooled to ambient temperature. The resultant brown suspension was diluted with 300 mL water and extracted with diethyl ether (2 x 200 mL). The organic phases were combined and dried over anhydrous sodium sulfate, filtered and concentrated under reduced pressure. The resultant oil was flash chromatographed with 15% ethyl acetate/hexanes to yield 1.78 g (60%) of the desired 3- (3-ETHOXYCARBONYLMETHOXY-4- methyl-phenyl)-piperidine-1-carboxylic acid benzyl ester as a clear oil. MS (LC-MS) 462.1 (M + NA) +. H NMR (400 MHz, CDCI3) 8 7.35 (m, 5H), 7.09 (d, 1 H), 6.76 (d, 1 H), 6.56 (s, 1H), 5.14 (m, 2H), 4.61 (s, 2H), 4.23 (m, 2H), 2.78 (q, 2H), 2.62 (m, 1H), 2.25 (s, 3H), 1.98 (m, 1H), 1.76 (m, 1H), 1.56 (m, 3H), 1.29 (t, 3H). A 250 mL Parr bottle was charged with 0.18g of 10% palladium on carbon (50% water) and covered with 20 mL ethanol. 3- (3-ETHOXYCARBONYLMETHOXY-4-METHYL- PHENYL)-PIPERIDINE-1-CARBOXYLIC acid benzyl ester (1.78g, 4.33 mmol) was dissolved in 50 mL ethanol and added to the catalyst suspension. The reaction was hydrogenated at 50 psi for 2 h. The catalyst was filtered through a celite plug. The filter cake was washed with 150 mL ethanol and the filtrated concentrated under reduced pressure. The resultant oil was taken up in 20 mL hot ethanol to which was added D-tartaric acid (650 mg, 4.33 mmol) in 10 mL hot ethanol. The solution was allowed to stir 24 h at ambient temperature. The white crystalline precipitate was collected by filtration to yield 1. 014G (55%) of (2-methyl-5-piperidin-3-yl-phenoxy)- acetic acid ethyl ester D-tartaric acid salt as a white crystalline solid. MS (LC-MS) 278.3 (M + H) +. 1 HNMR (400 MHz, DMSOd6) 8 7. 11 (d, 1 H), 6.78 (d, 1 H), 6.44 (s, 1 H), 4.16 (q, 2H), 3.81 (s, 2H), 3.21 (t, 2H), 2.78 (m, 2H), 2.10 (s, 3H), 1.81 (m, 2H), 1.69 (m, 1H), 1.56 (m, 1H), 1.51 (s, 6H), 1.14 (t, 3H). HPLC analysis : Chiralpak AD, 1 mL/min, 5% isopropanol/heptane 0.2% diethylamine, rt = 3.18. ee = 98.9. (2-METHYL-5-PIPERIDIN-3-YL-PHENOXY)-ACETIC acid ethyl ester D-tartaric acid salt was carried on using procedures analogous to those described in Example 12 to give the title compound, (R)- (2-METHYL-5- {1- [4-METHYL-2- (4-TRIFLUOROMETHYL-PHENYL)-THIAZOLE- 5-CARBONYL]-PIPERIDIN-3-YL}-PHENOXY)-ACETIC acid. MS (LC-MS) 450.1 (M-H)-. 1H NMR (400 MHz, CD30D) 8 8.13 (d, 2H), 7.78 (d, 2H), 7.06 (m, 1H), 6. 75 (brm, 2H), 4.66 (brs, 2H), 2.76 (t, 1 H), 2.48 (s, 3H), 2.20 (s, 3H), 2.04 (d, 1H), 1.83 (m, 2H), 1.67 (m, 1H).

Reference： [1]Current Patent Assignee: PFIZER INC - WO2004/48334, 2004, A1 Location in patent: Page 170-171

15
[ 147-71-7 ]
[ 112101-81-2 ]
[ 863666-27-7 ]

Yield	Reaction Conditions	Operation in experiment
	In methanol; DMF (N,N-dimethyl-formamide); at 60℃; for 6h;Purification / work up;	25 gm of R- (-)-5- (2-aminopropyl)-2-methoxybenzenesulfonamide (m. p.: 170C) was dissolved in solvent mixture of 250 ml methanol and 50 ml N, N-dimethylformamide on heating. 16.9 gm D (-) tartaric acid was added at 60 C, maintained the temperature for 6 hours. The crystals formed were collected by filtration, washed with methanol. The crystals, which were collected out (wet), were stirred for 1/2 AN hour with 75 ml methanol. The solid was filtered off and washed with methanol, affording 32.7 gm tartarate salt of R- (-)-5- (2- aminopropyl)-2-methoxybenzenesulfonamide. Melting point: 198 C(D); [?] D25 (C = 1.0,H2O) : -20.5
	In methanol; water; at 65℃; for 6 - 8h;Purification / work up;	10 gm of R- (-)-5- (2-aminopropyl)-2-methoxybenzenesulfonamide (m. p. =170C) was dissolved in 100 ml solvent mixture of methanol and water (9.3 : 0.7 V/V) on heating, 6.8 gm D (-) tartaric acid was added at 65 C, maintained the temperature for 6 hours. The crystals formed were collected by filtration, washed with methanol and dried to provide 8.9 gm tartarate salt OF R- (-)-5- (2-AMINOPROPYL)-2-METHOXYBENZENESULFONAMIDE. <P>MELTING POINT : 198C (D) [?] D25 (C = 1.0, H20) : -20. 6 Example : 18 R- (-)-5- (2-AMINOPROPYL)-2-METHOXYBENZENESULFONAMIDE tartarate 10 gm of R- (-)-5- (2-AMINOPROPYL)-2-METHOXYBENZENESULFONAMIDE (m. p.: 172C) was dissolved in 100 ml a solvent mixture of methanol and water (9: 1 V/V) on heating, 6.8 gm D (-) tartaric acid was added at 65C, maintain it for 8 hours. Crystals formed were collected by filtration washed with methanol and dried to provide 10.9 gm tartarate salt OF R- (-)-5- (2-AMINOPROPYL)-2-METHOXY BENZENESULFONAMIDE. MELTING POINT : 198C (D); [OT] 25 (C = 1. 0, HO) : -20. 6

Reference： [1]Patent: WO2004/58694,2004,A1 .Location in patent: Page 10
[2]Patent: WO2004/58694,2004,A1 .Location in patent: Page 10-11

16
[ 147-71-7 ]
[ 127733-40-8 ]
[ 127733-47-5 ]
[ 384824-37-7 ]
C₄H₆O₆*C₁₀H₉F₆N [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
	In methanol; for 12.5h;Heating / reflux;	0.94 g (3.64 mmol, 1 eq) of optically active 1-(3,5-bis-trifluoromethylphenyl)ethylamine (5a, enantiomer ratio/S form:R form=7.4:1) and 0.55 g (3.64 mmol, 1 eq) of d-tartaric acid were added to 30 ml of methanol, followed by stirring for 30 minutes under reflux, allowing to cool to room temperature and stand for one half day. The precipitated crystals were filtered, washed with a small amount of methanol and vacuum dried to obtain 1.01 g of crystals having the structure represented by the formula below and 0.48 g of mother liquor. They were converted to the free bases with 0.5 N aqueous NaOH and analyzed by chiral GC. With this, respective ee were found to be 91.4% ee (major form is the S form) and 43.8% ee (major form is the S form). [C00040] [00182] 1H-NMR (TMS, DMSO): 1.45 (d, 6.8 Hz, 3H), 3.92 (s, 2H), 4.52 (q, 6.8 Hz, 1H), 6408 (s, 1H), 8.19 (s, 2H).

Reference： [1]Patent: US6797842,2004,B2 .Location in patent: Page column 32-33

17
[ 147-71-7 ]
[ 88150-42-9 ]
S(-) amlodipine hemi D(-) tartarate [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
40.0%	In N,N-dimethyl acetamide; at 22 - 70℃; for 4.5h;	A solution ofD-Tartaric acid (9.48 kg, 63.15 moles) in DMAC (104.2 kg) is added to a slurry of (RS)-<strong>[88150-42-9]Amlodipine</strong> free base (24.9 kg, 60.9 moles) in N,N-Dimethylacetamide (DMAC, 104.3 kg). The reaction mixture is agitated and heated to about 70 C. The reaction mass is held for one hour with agitation at about 70 C. The resulting slurry is then cooled with agitation to about 22 C over 2.5 to 3 hours with a linear cooling profile at about 0.30 C/min. The slurry is held with agitation at about 22 C for about 0.5 h. The solid is isolated by filtration, washed by re-slurrying with DMAC followed by a displacement wash with MTBE. The wet cake is dried at about 45 C in vacuo to produce (S)-<strong>[88150-42-9]Amlodipine</strong>-hemi-D-Tartrate-DMAC solvate (13.92 kg, 24.37 moles, 40.0 % yield).
34.6 - 40.8%	In dimethyl sulfoxide; at 20℃;	To a stirred solution of 100 gm (0.245 moles) of RS amlodipine in 500 ml DMSO was added a solution of 9.2 gm (0.06 moles, 0.25 eq) of D(-) tartaric acid in 500 ml DMSO. The solid starts separating from clear solution within 5-10 ml. This was stirred at room temperature overnight and solid was filtered off, washed with =etone and dried to give 47.5 gm (34.6%) S(-) amlodipine hemi D(-) tartarate mono DMSO solvate. mp. 159-161 C., 99.5% d.e. by chiral HPLC.To a stirred solution of 100 gm (0.245 moles) of RS amlodipine in 250 ml DMSO was added a solution of 9.2 gm (0.06 moles, 0.25 eq) of D(-) tartaric acid in 250 ml DMSO. The solid starts separating from clear solution within 5-10 wins. This was stirred at room temperature overnight and solid was filtered off, washed with acetone and dried to give 56.2 gm (40.8) S (-) amlodipine hemi D(-) tartarate mono DMSO solvate. mp. 159-161 C., 98.4% d.e. by chiral HPLC.

Reference： [1]Patent: WO2005/97191,2005,A2 .Location in patent: Page/Page column 93
[2]Patent: US6846932,2005,B1 .Location in patent: Page column 6

18
[ 147-71-7 ]
[ 88150-42-9 ]
[ 67-68-5 ]
(4-S)-2-[(2-aminoethyl)oxy]methyl}-4-(2-chlorophenyl)-6-methyl-1,4-dihydropyridine-3,5-dicarboxylate hemi D(-) tartarate mono DMSO solvate [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
34.6 - 40.8%	Product distribution / selectivity;	To a stirred solution of100gm (0.245 moles) of RS amlodipine in 500ml DMSO was added a solution of 9.2 gm (0.06 moles, 0.25 eq)of D (-) tartaric acid in 500 ml DMSO. The solid starts separating from clear solution within 5-10 mins. This was stirred at room temperature overnight and solid was filtered off, washed with acetone and dried to give47.5gm (34.6%) S (-)amlodipine hemi D (-) tartarate mono DMSO solvate. mp. 159-161 C, 99.5% d. e. by chiralEPLC;. Example 5: S (-) amlodipine hemiD (-) tartarate mono DMSO solvate from RSamlodipine; To a stirred solution of100gm (0.245 moles) of RS amlodipine in 250ml DMSO was added a solution of 9.2 gm (0.06 moles, 0.25 eq)of D (-) tartaric acid in 250 ml DMSO. The solid starts separating from clear solution within 5-10 mins. This was stirred at room temperature overnight and solid was filtered off, washed with acetone and dried to give 56.2 gm (40.8 %) S (-) amlodipine hemi D (-) tartarate mono DMSO solvate. mp.159-161 C, 98.4% d. e. by chiralHPLC.

Reference： [1]Patent: WO2005/49571,2005,A1 .Location in patent: Page/Page column 5-6

19
[ 147-71-7 ]
[ 152459-95-5 ]
[ 862366-43-6 ]

Yield	Reaction Conditions	Operation in experiment
	In ethanol at 90℃;	20 Example 20; 4-[(4-Methyl-1-piperazinyl)methyl]-N-[4-methyl-3-[[4-(3-pyridinyl)-2- pyrimidinyl] amino] phenyl]-benzamide, (D)-(-)-tartrate; A solution of (2S, 3S) -2, 3-dihydroxy-butanedioic acid (tartaric acid; Fluka, Buchs, Switzerland; 606.5 mg, 1.97 mmol) in ethanol (90 mL) is added to a solution of 4- [ (4-methyl- 1-piperazinyl) methyl]-N-[4-methyl-3-[[4-(3-pyridinyl)-2-pyrimidinyl] amino] phenyl]-benzamide (1.975 g, 4 mmol) in hot ethanol (150 mL at 90°C). The hot solution is slowly cooled to 20°C to afford, after filtering and drying, 4- [ (4-methyl-1-piperazinyl) methyl]-N- [4-methyl-3- [ [4- (3- pyridinyl)-2-pyrimidinyl] amino] phenyl]-benzamide, tartrate as a crystalline solid, having the following analytical properties: Analysis found: C, 60.54 ; H, 6.08 ; N, 14.37 ; O, 18. 89%. H2O, 1.32%. Calculated for C33H37N707-0. 50 EtOH-0. 50 H20 : C, 60.43 ; H, 6.12 ; N, 14.51 ; O, 18.94%. H20, 1.33%.

Reference： [1]Current Patent Assignee: Novartis (w/o Sandoz); NOVARTIS AG - WO2005/75454, 2005, A2 Location in patent: Page/Page column 11

20
[ 147-71-7 ]
[ 106650-56-0 ]
[ 259729-92-5 ]

Yield	Reaction Conditions	Operation in experiment
98%	In water; acetone; toluene for 0.5h; Heating / reflux;	5.2 An exemplary method of preparing the (D) -tartrate salt of racemic didesmethylsibutramine ((R/S)-DDMS (D) -TA) is shown below in Scheme 2. The (L)- tartrate salt of racemic didesmethylsibutramine ((R/S)-DDMS (L) -TA) can be prepared in an analogous manner. /i-BuMgBr NaBH4 CN Toluene/ JLJ [ T . MeOH ci Cl zW Nv MeOH cl CCBC (D) or USD)-Tartaric Acid Cl Toluene Cil 2 (R/S)-DDMS. (D)-or (L)-Tartarate (R/S)-DDMS (R/S)-DDMS-(D)-TA or (R/S)-DDMS- (L)-TA Scheme 2 Following Scheme 2, a mixture of racemic didesmethylsibutramine (15.3 g) and toluene (160 ml) was heated to 70-80°C and (D) -tartaric acid (9.1 g) in water (20 ml) and acetone (10 ml) was added slowly. The resulting mixture was refluxed for 30 minutes, after which the water and acetone were removed by distillation. The resulting mixture was cooled to room temperature to provide a slurry which was then filtered. The resulting wet cake was washed two times with MTBE (20 ml x 2) and dried to yield (R/S)-DDMS- (D) -TA (22.5 g, 98 %). NMR (DMSO-d6) :'H (6), 0.6-0. 92 (m, 6H), 0.92-1. 1 (m, 1H), 1.1-1. 3 (m, 1H), 1.5- 1.8 (m, 2H), 1.8-2. 1 (m, 1H), 2.1-2. 4 (m, 3H), 2.4-2. 6 (m, 1H), 3.4-3. 6 (m, 1H), 3.9-4. 2 (s, 2H), 6.4-7. 2 (b, 6H, OH, COOH and NH2), 7.3-7. 6 (m, 4H). 13C (8) : 15.5, 21.1, 23.3, 23.7, 31.5, 37.7, 39.7, 54.5, 72.1, 128,129. 7,131. 3,142. 2,174. 6.
98%	In water; acetone; toluene at 70 - 80℃; for 0.5h; Heating / reflux;	2 (D)-or (L)-Tartarate (R/S)-DDMS (R/S)-DDMS (D) -TA or (R/S)-DDMS- (L) -TA A mixture of racemic didesmethylsibutramine (15.3 g) and toluene (160 mL) was heated to 70-80°C and (D) -tartaric acid (9.1 g) in water (20 mL) and acetone (10 mL) was added slowly. The resulting mixture was refluxed for 30 minutes, after which the water and acetone were removed by distillation. The resulting mixture was cooled to room temperature to provide a slurry which was then filtered. The resulting wet cake was washed two times with MTBE (20 mL x 2) and dried to yield (R/S)-DDMS- (D) -TA (22.5 g, 98 %). NMR (DMSO-d6) : in (6), 0.6-0. 92 (m, 6H), 0.92-1. 1 (m, 1H), 1.1-1. 3 (m, 1H), 1.5-1. 8 (m, 2H), 1.8-2. 1 (m, 1H), 2.1-2. 4 (m, 3H), 2.4-2. 6 (m, 1H), 3.4-3. 6 (m, 1H), 3.9-4. 2 (s, 2H), 6.4-7. 2 (b, 6H, OH, COOH andNH2), 7.3-7. 6 (m, 4H). 13C (6) : 15.5, 21.1, 23.3, 23.7, 31.5, 37.7, 39.7, 54.5, 72.1, 128,129. 7,131. 3,142. 2,174. 6.

Reference： [1]Current Patent Assignee: Sumitomo Chemical (w/o Dongwoo Fine-Chem); Sumitomo Pharma (in: Sumitomo Chemical); SUMITOMO CHEMICAL COMPANY LIMITED - WO2005/72715, 2005, A1 Location in patent: Page/Page column 29-30
[2]Current Patent Assignee: SUMITOMO CHEMICAL COMPANY LIMITED; Sumitomo Chemical (w/o Dongwoo Fine-Chem); Sumitomo Pharma (in: Sumitomo Chemical) - WO2005/79851, 2005, A2 Location in patent: Page/Page column 69-70

21
[ 147-71-7 ]
[ 88150-42-9 ]
(S)-amlodipine-hemi-D-tartrate [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
78.38%	In water; N,N-dimethyl-formamide; at 20℃; for 4.5h;Resolution of racemate;Product distribution / selectivity;	Example-9 (R)-AmIodipine-D-hemitartrate dimethyl formamide solvate(RS)-<strong>[88150-42-9]Amlodipine</strong> (16 gm, 0.04 moles) was dissolved in 140 ml dimethyl formamide water mixture (15 % water in DMF).To this mixture, a solution of D-tartaric acid, prepared by dissolving tartaric acid(1.47g, 0.01 moles) in 20 ml DMF + water mixture (proportion as referred above) was added drop wise in 30 min. The mixture was stirred for 4 hr at room temperature after addition. The slurry was filtered and the residual solid was washed with acetone (10 ml) and dried to give the title productYield = 7.4 gm.%Yield: 78.38%. Melting point; 137C.Optical Purity by Chiral HPLC: 99.50%
40%	In N,N-dimethyl acetamide; at 22 - 70℃; for 4 - 4.5h;	Formation of (S)-Amlodpine-hemi-D-Tartrate DMAC Solvate from (RS)-<strong>[88150-42-9]Amlodipine</strong> Free Base A solution of D-Tartaric acid (9.48 kg, 63.15 moles) in DMAC (104.2 kg) was added to a slurry of (RS)-<strong>[88150-42-9]Amlodipine</strong> free base SEP-174677 (24.9 kg, 60.9 moles) in N, N- Dimethylacetamide (DMAC, 104.3 kg). The reaction mixture was agitated and heated to about 70C. The reaction mass is held for one hour with agitation at about 70C. The resulting slurry was then cooled with agitation to about 22C over 2.5 to 3 hours with a linear cooling profile at about 0. 30C/min. The slurry was held with agitation at about 22C for about 0.5 hr. The solid was isolated by filtration, washed by re-slurrying with DMAC followed by a displacement wash with MTBE. The wet cake was dried at about 45C in vacuo to produce (S)-<strong>[88150-42-9]Amlodipine</strong>-hemi-D-Tartrate-DMAC solvate (13.92 kg, 24.37 moles, 40.0 % yield).
40.0%	In ISOPROPYLAMIDE; at 70℃; for 1h;Resolution of racemate;	A solution of D-Tartaric acid (9.48 kg, 63.15 moles) in DMAC (104.2 kg) is added to a slurry of (RS)-<strong>[88150-42-9]Amlodipine</strong> free base (24.9 kg, 60.9 moles) in N, N-Dimethylacetamide (DMAC, 104.3 kg). The reaction mixture is agitated and heated to about 70 C. The reaction mass is held for one hour with agitation at about 70 C. The resulting slurry is then cooled with agitation to about 22 C over 2.5 to 3 hours with a linear cooling profile at about 0. 30 C/min. The slurry is held with agitation at about 22 C for about 0.5 h. The solid is isolated by filtration, washed by re-slurrying with DMAC followed by a displacement wash with MTBE. The wet cake is dried at about 45 C in vacuo to produce (S)-<strong>[88150-42-9]Amlodipine</strong>-hemi-D-Tartrate-DMAC solvate (13.92 kg, 24.37 moles, 40.0 % yield).

40.0%

In ISOPROPYLAMIDE; at 22 - 70℃; for 4 - 4.5h;Resolution of racemate;

A solution of D-Tartaric acid (9.48 kg, 63.15 moles) in DMAC (104.2 kg) is added to a slurry of (RS)-[88150-42-9]Amlodipine free base (24.9 kg, 60.9 moles) in N,N-Dimethylacetamide (DMAC, 104.3 kg). The reaction mixture is agitated and heated to about 70 C. The reaction mass is held for one hour with agitation at about 70 C. The resulting slurry is then cooled with agitation to about 22 C over 2.5 to 3 hours with a linear cooling profile at about 0.30 C/min. The slurry is held with agitation at about 22 C for about 0.5 h. The solid is isolated by filtration, washed by re-slurrying with DMAC followed by a displacement wash with MTBE. The wet cake is dried at about 45 C in vacuo to produce (S)-[88150-42-9]Amlodipine-hemi-D-Tartrate-DMAC solvate (13.92 kg, 24.37 moles, 40.0 % yield).

Reference： [1]Patent: WO2006/43148,2006,A1 .Location in patent: Page/Page column 16
[2]Patent: WO2005/70462,2005,A2 .Location in patent: Page/Page column 32-33
[3]Patent: WO2005/79772,2005,A2 .Location in patent: Page/Page column 69
[4]Patent: WO2005/99699,2005,A1 .Location in patent: Page/Page column 91-92; sheet 1/7; figure 1

22
[ 147-71-7 ]
[ 111470-99-6 ]
(S)-amlodipine-hemi-D-tartrate [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
		Detailed Process Description for (S)-Amlodipine Hemi-D-Tartrate DMAC solvate: The following is a typical batch description for the process using the racemic besylate salt as an input. 1. N, N-Dimethylacetamide (DMAC) (152.7 kg) was charged to a 100 gal reactor (T- 110A). 2. D-Tartaric acid (13. 88 kg) was charged slowly to T-110A. 3. The solution in T-11 OA was mixed and held for use later in the batch. 4. (R -<strong>[111470-99-6]Amlodipine besylate</strong> (49.81 kg) was charged to a 200 gal reactor (R-120), followed by methyl t-butyl ether (MTBE) (239.3 kg). 5. Aqueous sodium hydroxide (IN) (137. 2kg) was added to R-120. 6. The contents of R-120 were agitated for 20-30 minutes and then the layers were allowed to separate for a minimum of 15 minutes. 7. The bottom aqueous layer was removed and USP water (66.0 kg) was charged to R- 120. 8. The contents of R-120 were agitated for a minimum of 20 minutes and then the layers were allowed to separate for a minimum of 15 minutes. 9. The bottom aqueous layer was removed and USP water (66.0 kg) was charged to R- 120. 10. The contents of R-120 were agitated for a minimum of 20 minutes and then the layers were allowed to separate for a minimum of 15 minutes. 11. The bottom aqueous layer was removed from R-120. 12. The contents of R-120 were polish filtered through a 3am cartridge filter to R- 110A, followed by a reactor and line rinse with MTBE (49.9 kg). 13. The contents of R-110A were concentrated under vacuum (maximum 50C) to a calculated volume (109 L). 14. DMAC (152. 8 kg) was charged to the contents ofR-110A. 15. The contents of R-11 OA were again concentrated under vacuum, this time until the batch temperature reached 45-55 C. The final volume was 208L. 16. R-110A contents were cooled to 20 to 25 C, followed by the addition of the previously prepared D-tartaric acid solution (166. 0kg) at 20-25 C over 20 to 30 minutes. 17. The mixture was heated to 68-72 C over 55 to 65 minutes, and held at this temperature for 55 to 65 minutes. 18. The reaction mixture was cooled to 21 to 23 C over 2 to 3 hours using a linear cooling profile and agitated at this temperature for 30 to 40 minutes. 19. The slurry was filtered on a centrifuge (CE-102) in one load and washed with DMAC (75.7 kg) and MTBE (59.9 kg). 20. The wet cake was discharged (20.33 kg) and dried in vacuum tray dryer (D-401) for a minimum of 6 hours at 45-50C to yield 20.086 kg of (S)-Amlodipine Hemi-D- Tartrate DMAC solvate.
	With sodium hydroxide; In tert-butyl methyl ether; ISOPROPYLAMIDE; water; at 20 - 72℃; for 5.66667 - 6.41667h;Resolution of racemate;	The following is a typical batch description for the process using the racemic besylate salt as an input. 1. NN-Dimethylacetamide (DMAC) (152.7 kg) was charged to a 100 gal reactor (T-110A). 2. D-Tartaric acid (13.88 kg) was charged slowly to T-110A. 3. The solution in T-11OA was mixed and held for use later in the batch. 4. (RS)-<strong>[111470-99-6]Amlodipine besylate</strong> (49.81kg) was charged to a 200 gal reactor (R-120), followed by methyl t-butyl ether (MTBE) (239.3 kg). 5. Aqueous sodium hydroxide (1 N) (137.2 kg) was added to R-120. 6. The contents of R-120 were agitated for 20-30 minutes and then the layers were allowed to separate for a minimum of 15 minutes. 7. The bottom aqueous layer was removed and USP water (66.0 kg) was charged to R-120. 8. The contents of R-120 were agitated for a minimum of 20 minutes and then the layers were allowed to separate for a minimum of 15 minutes. 9. The bottom aqueous layer was removed and USP water (66.0 kg) was charged to R-120. 10. The contents of R-120 were agitated for a minimum of 20 minutes and then the layers were allowed to separate for a minimum of 15 minutes. 11. The bottom aqueous layer was removed from R-120. 12. The contents of R-120 were polish filtered through a 3 " m cartridge filter to R- 110A, followed by a reactor and line rinse with MTBE (49.9 kg). 13. The contents of R-110A were concentrated under vacuum (maximum 50No.C) to a calculated volume (109 L). 14. DMAC (152.8 kg) was charged to the contents of R-110A. 15. The contents of R-110A were again concentrated under vacuum, this time until the batch temperature reached 45-55No.C. The final volume was 208 L. 16. R-110A contents were cooled to 20 to 25No.C, followed by the addition of the previously prepared D-tartaric acid solution (166.0 kg) at 20-25No.C over 20 to 30 minutes. 17. The mixture was heated to 68-72No.C over 55 to 65 minutes, and held at this temperature for 55 to 65 minutes. 18. The reaction mixture was cooled to 21 to 23No.C over 2 to 3 hours using a linear cooling profile and agitated at this temperature for 30 to 40 minutes. 19. The slurry was filtered on a centrifuge (CE-102) in one load and washed with DMAC (75.7 kg) and MTBE (59.9 kg). 20. The wet cake was discharged (20.33 kg) and dried in vacuum tray dryer (D-401) for a minimum of 6 hours at 45-50No.C to yield 20.086 kg of (S)-Amlodipine Hemi-D-Tartrate DMAC solvate.

Reference： [1]Patent: WO2005/79772,2005,A2 .Location in patent: Page/Page column 69
[2]Patent: WO2005/99699,2005,A1 .Location in patent: Page/Page column 92-93; sheet 1/7; figure 1; sheet 2/7; figure 2

23
[ 147-71-7 ]
[ 2353-33-5 ]
decitabine (+)-L-tartate [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
	In methanol; at 30 - 55℃; for 0.5h;Heated in sonicator;	In still some embodiments, decitabine salts were prepared from weak acids (3.0

Reference： [1]Patent: US2006/69060,2006,A1 .Location in patent: Page/Page column 15

24
[ 147-71-7 ]
[ 104641-59-0 ]
[ 104712-66-5 ]

Yield	Reaction Conditions	Operation in experiment
	In methanol; diethyl ether;	This material was treated with 2.5 g of (2S, 3S) -tartaric acid in MeOH/ether to obtain 3.65 g of the tartrate salt [a] o =-11. 3 (c=1, H20) 2. 2 [alpha]22D =-11. 5 (c=1, H2O), Sleevi et al. J. Med. Chem., (1991), Vol 34, n4, 1314-1328).

Reference： [1]Patent: WO2003/87094,2003,A2 .Location in patent: Page/Page column 34

25
[ 62813-09-6 ]
[ 147-71-7 ]
[ 886588-62-1 ]

Yield	Reaction Conditions	Operation in experiment
	In ethanol at 90℃; for 0.5h;
	In ethanol; acetic acid at 50 - 90℃; for 0.5h; Industry scale;	1.c A solution of 11.16 kg D-(-)-tartaric acid (74.38 mol) in 50 litres of absolute ethanol heated to 50° C. is metered at 90° C. into the acylation reaction solution. This is rinsed with 10 litres of absolute ethanol and stirred for 30 minutes at 90° C., during which time the product crystallises out. After cooling to 5° C. the product is centrifuged off and washed with absolute ethanol.

Reference： [1]Current Patent Assignee: C.H. Boehringer Sohn AG & Co. KG - WO2006/48427, 2006, A1 Location in patent: Page/Page column 6; 8
[2]Current Patent Assignee: C.H. Boehringer Sohn AG & Co. KG - US2007/27168, 2007, A1 Location in patent: Page/Page column 4

26
[ 147-71-7 ]
[ 321-38-0 ]
(RS)-N,N-dimethyl-3-hydroxy-3-(1-naphthyloxy)-3-(2-thienyl)propylamine/D-tartrate [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
75%	Stage #1: 3-(N,N-dimethylamino)-1-(thien-2-yl)propan-1-ol; 1-Fluoronaphthalene With potassium hydroxide In dimethyl sulfoxide at 100℃; for 2h; Stage #2: D-tartaric acid In water Heating / reflux;	1 Example 1 : (jR5)-N,N-dimethyl-3-(naphthyloxy)-3-(2-thienyl)propylamine-D-tartrate.; A mixture of N,N-dimethyl-3-hydroxy-3-(2-thienyl)propylamine (370 g), potassium hydroxide (336 g) and 1-fluoronaphthalene (284 ml) in dimethylsulfoxide (2 1) is stirred at 100 0C for 2 hours. The mixture is then cooled down to lab temperature, diluted with water (4 1) and toluene (2 1). The organic phase is separated, shaken with water and evaporated. A hot solution of D-tartaric acid (252 g) in water (3 1) is added to the evaporation residue under stirring. After cooling down, the precipitated product is sucked off, washed with water and dried. The yield is 687 g (75 %).

Reference： [1]Current Patent Assignee: ADVENT INTERNATIONAL CORPORATION - WO2006/45255, 2006, A1 Location in patent: Page/Page column 5

27
[ 147-71-7 ]
[ 302962-49-8 ]
N-(2-chloro-6-methylphenyl)-2-((6-(4-(2-hydroxyethyl)-1-piperazinyl)-2-methyl-4-pyrimidinyl)amino)-1,3-thiazole-5-carboxamide D-tartaric acid salt [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
	In ethanol at 70℃;	5.1; 5.2 EXAMPLE 5; TARTARIC ACID SALTS OF COMPOUND I; EXAMPLE 5.1; HIGH THROUGHPUT CRYSTALLIZATION SCREENING; [00326] The following crystalline forms of tartaric acid salts were prepared by high throughput crystallization, according to the general procedure described in Example 1.1:[00327] Larger quantities of the tartaric acid salts were prepared according to the following procedures:; EXAMPLE 5.2; FORM V.I; [00328] A mixture was prepared by combining 0.82 g Compound 1, 15 mL EtOH, and 250 mg D-tartaric acid. The mixture was heated to 700C to afford a thin slurry, cooled to 4O0C, and maintained at 400C overnight. The mixture was cooled, and filtered. The solid material was dried to afford 0.9O g of crystalline material.ELEMENTAL ANALYSIS:

Reference： [1]Current Patent Assignee: BRISTOL-MYERS SQUIBB CO - WO2007/35874, 2007, A1 Location in patent: Page/Page column 73-74

28
[ 147-71-7 ]
[ 77-76-9 ]
[ 126581-14-4 ]

Yield	Reaction Conditions	Operation in experiment
100%	With toluene-4-sulfonic acid In deuteromethanol
	With cyclohexane; toluene-4-sulfonic acid In methanol Heating;
	With toluene-4-sulfonic acid In methanol at 65℃; for 16h; Inert atmosphere;	To a stirred solution of (2S,3S)-tartaric acid (22; 100 g) in MeOH (20mL) were added a catalytic amount of TsOH and 2,2-dimethoxypropane(2 equiv). The mixture was refluxed for 16 h until the starting material was consumed (TLC), then concentrated under reduced pressureand purified by column chromatography (hexanes-EtOAc, 9:1) togive 22.1 as a colorless liquid.

Reference： [1]Bastos, Carina A.; Gomes, Cláudia R. B.; De Souza, Marcus V. N.; De Oliveira, Marcone A. L. [Journal of the Brazilian Chemical Society, 2015, vol. 26, # 5, p. 887 - 898]
[2]Gupta, Shuchi; Rajagopalan, Murali; Alhamadsheh, Mamoun M.; Tillekeratne, L. M. Viranga; Hudson, Richard A. [Synthesis, 2007, # 22, p. 3512 - 3518]
[3]Konda, Saidulu; Khatravath, Mahender; Mallurwar, Naveen Kumar; Rao, Pallavi; Sripelly, Shivashankar; Iqbal, Javed; Arya, Prabhat [Synthesis, 2016, vol. 48, # 11, p. 1663 - 1683]

29
[ 147-71-7 ]
[ 7732-18-5 ]
[ 62-54-4 ]
calcium l-tartrate*4H₂O [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
98.95%	In acetic acid addn. of 15 ml 95 % ethanol to mixture of 50 ml 1 % l-tartaric acid soln. and 10 ml Ca(CH3CO2)2 soln. (preparation for 1 l: 32 g CaCO3, 120 ml pure acetic acid, rest H2O); add. of further 15 ml 95 % ethanol after 24 hs; complete pptn. after 48 hs;; washing 3 times by decantation, pressing on filter paper, drying at ambient temp.;;
	In acetic acid addn. of 1 l acetic Ca(CH3CO2)2 soln. (32 g CaCO3, 120 ml pure acetic acid, rest H2O) to 2 l 1 % d-tartaric acid soln.; complete pptn. after 24 hs;; washing 3 times by decantation, pressing on filter paper, drying at ambient temp.;;
	In acetic acid

Reference： [1]Francois, M.; Lormand, C. [Journal de Pharmacie et de Chimie, 1923, vol. 28, p. 433 - 442]
[2]Francois, M.; Lormand, C. [Journal de Pharmacie et de Chimie, 1923, vol. 28, p. 433 - 442]
[3][Gmelin Handbuch der Anorganischen Chemie, Gmelin Handbook: Ca: MVol.B3, 162, page 1014 - 1016]

30
[ 147-71-7 ]
[ 88150-42-9 ]
[ 68-12-2 ]
(R)-amlodipine-D-hemitartrate dimethylformamide solvate [ No CAS ]
[ 103129-82-4 ]

Yield	Reaction Conditions	Operation in experiment
78.38%	In water; at 20℃; for 4.5h;Product distribution / selectivity;	EXAMPLE-9 (R)-<strong>[88150-42-9]Amlodipine</strong>-D-hemitartrate Dimethyl Formamide Solvate (RS)-<strong>[88150-42-9]Amlodipine</strong> (16 gm, 0.04 moles) was dissolved in 140 ml dimethyl formamide water mixture (15% water in DMF). To this mixture, a solution of D-tartaric acid, prepared by dissolving tartaric acid (1.47 g, 0.01 moles) in 20 ml DMF+water mixture (proportion as referred above) was added drop wise in 30 min. The mixture was stirred for 4 hr at room temperature after addition. The slurry was filtered and the residual solid was washed with acetone (10 ml) and dried to give the title product: Yield=7.4 gm. % Yield: 78.38%. Melting point; 137 C. Optical Purity by Chiral HPLC: 99.50%

Reference： [1]Patent: US2008/262239,2008,A1 .Location in patent: Page/Page column 7

31
[ 147-71-7 ]
[ 88150-42-9 ]
[ 57-13-6 ]
S-(-)-amlodipine D-(-)-tartrate urea complex [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
72 - 85%	In water; isopropyl alcohol; at 50℃; for 1h;Product distribution / selectivity;	Example 2 to 8: Preparation of S-(-)-anilodipine 'D-(-)-tartrate ' iirea complex (compound of formula (III))The procedure similar to that of Example 1 (1-1) was repeated using the respective organic solvents listed in Table 1, under the condition that the volume of the mixed solvent (an organic solvent : water is 3 : 1 by volume) was <n="10"/>8 ml per 1 g of amlodipine, while the amounts of D-(-)-tartaric acid and urea were 0.25 and 1 mole equivalent respectively based on 1 mole of amlodipine, to obtain the title compound.<Table 1>; Example 9 to 10: Preparation of S-(-)-amlodipine ' D-(-)-tartrate ? urea complex (compound of formula (III))The procedure similar to that of Example 1 (1-2) with the S-(~)- amlodipine-D-(-)-tartrate-urea complex obtained in Example 7 was repeated using the respective organic solvents as listed in Table 2, under the condition that the volume of the mixed solvent (an organic solvent : water is 2 : 1 by volume) used was 8 ml per 1 g of the complex, to obtain the title compound in purified forms as listed in Table 2.<Table 2>
68 - 82%	In water; acetonitrile; at 50℃; for 1h;Product distribution / selectivity;	Example 2 to 8: Preparation of S-(-)-anilodipine 'D-(-)-tartrate ' iirea complex (compound of formula (III))The procedure similar to that of Example 1 (1-1) was repeated using the respective organic solvents listed in Table 1, under the condition that the volume of the mixed solvent (an organic solvent : water is 3 : 1 by volume) was <n="10"/>8 ml per 1 g of amlodipine, while the amounts of D-(-)-tartaric acid and urea were 0.25 and 1 mole equivalent respectively based on 1 mole of amlodipine, to obtain the title compound.<Table 1>; Example 9 to 10: Preparation of S-(-)-amlodipine ' D-(-)-tartrate ? urea complex (compound of formula (III))The procedure similar to that of Example 1 (1-2) with the S-(~)- amlodipine-D-(-)-tartrate-urea complex obtained in Example 7 was repeated using the respective organic solvents as listed in Table 2, under the condition that the volume of the mixed solvent (an organic solvent : water is 2 : 1 by volume) used was 8 ml per 1 g of the complex, to obtain the title compound in purified forms as listed in Table 2.<Table 2>
67%	In acetic acid methyl ester; water; at 50℃; for 1h;Product distribution / selectivity;	Example 2 to 8: Preparation of S-(-)-anilodipine 'D-(-)-tartrate ' iirea complex (compound of formula (III))The procedure similar to that of Example 1 (1-1) was repeated using the respective organic solvents listed in Table 1, under the condition that the volume of the mixed solvent (an organic solvent : water is 3 : 1 by volume) was <n="10"/>8 ml per 1 g of amlodipine, while the amounts of D-(-)-tartaric acid and urea were 0.25 and 1 mole equivalent respectively based on 1 mole of amlodipine, to obtain the title compound.<Table 1>

67%	In water; tert-butyl alcohol; at 50℃; for 1h;Product distribution / selectivity;	Example 2 to 8: Preparation of S-(-)-anilodipine 'D-(-)-tartrate ' iirea complex (compound of formula (III))The procedure similar to that of Example 1 (1-1) was repeated using the respective organic solvents listed in Table 1, under the condition that the volume of the mixed solvent (an organic solvent : water is 3 : 1 by volume) was <n="10"/>8 ml per 1 g of amlodipine, while the amounts of D-(-)-tartaric acid and urea were 0.25 and 1 mole equivalent respectively based on 1 mole of amlodipine, to obtain the title compound.<Table 1>
64%	In water; iso-butanol; at 50℃; for 1h;Product distribution / selectivity;	Example 2 to 8: Preparation of S-(-)-anilodipine 'D-(-)-tartrate ' iirea complex (compound of formula (III))The procedure similar to that of Example 1 (1-1) was repeated using the respective organic solvents listed in Table 1, under the condition that the volume of the mixed solvent (an organic solvent : water is 3 : 1 by volume) was <n="10"/>8 ml per 1 g of amlodipine, while the amounts of D-(-)-tartaric acid and urea were 0.25 and 1 mole equivalent respectively based on 1 mole of amlodipine, to obtain the title compound.<Table 1>
63%	In 1,4-dioxane; water; at 50℃; for 1h;Product distribution / selectivity;	Example 2 to 8: Preparation of S-(-)-anilodipine 'D-(-)-tartrate ' iirea complex (compound of formula (III))The procedure similar to that of Example 1 (1-1) was repeated using the respective organic solvents listed in Table 1, under the condition that the volume of the mixed solvent (an organic solvent : water is 3 : 1 by volume) was <n="10"/>8 ml per 1 g of amlodipine, while the amounts of D-(-)-tartaric acid and urea were 0.25 and 1 mole equivalent respectively based on 1 mole of amlodipine, to obtain the title compound.<Table 1>
25%	In propan-1-ol; water; at 50℃; for 1h;Product distribution / selectivity;	Example 2 to 8: Preparation of S-(-)-anilodipine 'D-(-)-tartrate ' iirea complex (compound of formula (III))The procedure similar to that of Example 1 (1-1) was repeated using the respective organic solvents listed in Table 1, under the condition that the volume of the mixed solvent (an organic solvent : water is 3 : 1 by volume) was <n="10"/>8 ml per 1 g of amlodipine, while the amounts of D-(-)-tartaric acid and urea were 0.25 and 1 mole equivalent respectively based on 1 mole of amlodipine, to obtain the title compound.<Table 1>
	In water; isopropyl alcohol; at 50℃; for 1h;Product distribution / selectivity;	Example 1; Preparation of S-(-)-amlodipine?D-(-)-tartrate?urea complex (Compound of Formula (III))(1-1) 50 g of urea was dissolved in 250 ml of water, added 600 ml of 2-propanol and 112.5 g of amlodipine thereto, and heated to 50 C. Added to the resulting mixture was 10.4 g of D-(-)-tartaric acid dissolved in 50 ml of water, followed by stirring at 50 C. for 1 hour. The resulting solution was slowly cooled to room temperature, and stirred for 15 hours, after which the solution was further cooled to 5 C., and stirred for 3 hours. The precipitate formed was filtered and washed with 2-propanol and dried at 50 C., to obtain a crude S-(-)-amlodipine?D-(-)-tartrate?urea complex as a yellow crystalline powder (51.6 g; yield: 73%).b.p.: 198.5 to 199.3 C.;[alpha]D25: -27.2 (c=0.1, DMF);optical purity (HPLC): 95.3% ee (enantiomeric excess).
	In water; isopropyl alcohol; at 5 - 50℃; for 19h;Product distribution / selectivity;	Example 1: Preparation of S~(-)-amIodipine ? D-(-)-tartrate urea complex (compound of formula (III))(1-1) 50 g of urea was dissolved in 250 ml of water, added 600 ml of 2- propanol and 112.5 g of amlodipine thereto, and heated to 50 C . Added to the resulting mixture was 10.4 g of D-(-)- tartaric acid dissolved in 50 ml of water, followed by stirring at 50 C for 1 hour. The resulting solution was slowly cooled to room temperature, and stirred for 15 hours, after which the solution was further cooled to 5 C , and stirred for 3 hours. The precipitate formed was <n="9"/>filtered and washed with 2-propanol and dried at 50 "C , to obain a crude USD-(-)- amlodipine-D-(-)-tartrate-urea complex as a yellow crystalline powder (51.6 g; yield: 73%). b.p.: 198.5 to 199.3 C ; [alpha]D25: -27.2 (c=0.1, DMF); optical purity (HPLC): 95.3 % ee (enantiomeric excess).(1-2) 50 g of S-(-)-amlodipine>D-(-)-tartrate<urea complex obtained in (1-1) was suspended in a mixture of 125 ml of 2-propanol and 125 ml of water and heated to 70 C to obtain a homogenous solution. 250 ml of 2-propanol was added thereto and resulting mixture was slowly cooled to room temperature, and stirred for 18 hours, and then, further cooled to 5 C and stirred for 3 hours. The precipitate formed was filtered, washed with 2-rhororhoanol, and dried at 50 "C , to obtain a highly pure form of the title compound as a yellow crystalline powder (45.1 g; yield: 90%). m.p.: 201.8 to 202.8 TC ; [alpha]D25: -30.6 (c=0.1, DMF); S-(-)-amlodipine optical purity (HPLC): 99.8 % ee; tartaric acid content (HPLC): 14.71 % (theoretic content: 14.60 %); urea content (HPLC): 5.75 % (theoretic content: 5.84 %);IH-NMR (DMSO-d6, ppm): delta 7.35 (d, 2H), 7.22 (m, 4H), 7.10 (m, 2H), 5.42 (br, 4H, urea -NH2), 5.3 (s, 2H), 4.63 (dd, 4H), 4.0 (q, 4H), 3.88 (s, 2H, tartaric acid-CH (OH)-), 3.61 (t, 4H), 3.50 (s, 6H), 2.97 (t, 4H), 2.31 (s, 6H), 1.10 (t, 6H); IR (KBr, cm"1): 3499, 3382, 3342, 3217, 2951, 1688, 1635, 1603, 1480,1423, 1285, 1207, 1104, 1044, 1025.

Reference： [1]Patent: WO2008/100023,2008,A1 .Location in patent: Page/Page column 8-9
[2]Patent: WO2008/100023,2008,A1 .Location in patent: Page/Page column 8-9
[3]Patent: WO2008/100023,2008,A1 .Location in patent: Page/Page column 8-9
[4]Patent: WO2008/100023,2008,A1 .Location in patent: Page/Page column 8-9
[5]Patent: WO2008/100023,2008,A1 .Location in patent: Page/Page column 8-9
[6]Patent: WO2008/100023,2008,A1 .Location in patent: Page/Page column 8-9
[7]Patent: WO2008/100023,2008,A1 .Location in patent: Page/Page column 8-9
[8]Patent: US2010/99884,2010,A1 .Location in patent: Page/Page column 3
[9]Patent: WO2008/100023,2008,A1 .Location in patent: Page/Page column 7-8

32
(+/-)-trans-1-Benzyl-4-(4-fluorophenyl)-3-(3,4-methylenedioxyphenoxymethyl)piperidine Hydrochloride [ No CAS ]
[ 147-71-7 ]
(+)-(3R,4S)-trans-3-[(1,3-Benzodioxol-5-yloxy)methyl]-4-(4-fluorophenyl)piperidine hydrochloride [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
	Stage #1: (+/-)-trans-1-Benzyl-4-(4-fluorophenyl)-3-(3,4-methylenedioxyphenoxymethyl)piperidine Hydrochloride With ammonia In chloroform; water Alkaline conditions; Stage #2: With hydrogen In ethanol at 40℃; for 2 - 3h; Stage #3: D-tartaric acid With ammonium chloride more than 3 stages;	Ex. 24 A suspension containing 9.1 g (0.02 mol) of ()-trans-1-benzyl-4-(4-fluorophenyl)-3-(3,4-methylenedioxyphenoxymethyl)piperidine hydrochloride in the mixture of 100 ml of chloroform and 50 ml of water is alkalinized to pH 9 by adding concentrated aqueous ammonia solution. After separation of the phases, the aqueous layer is extracted with 20 ml of chloroform. The combined organic phase is dried over magnesium sulfate and, after filtering the drying agent the solution is evaporated to solvent-free. The evaporation residue is dissolved in 120 ml of ethanol and hydrogenated in an autoclave in the presence of 0.8 g of 10% palladium-on-carbon catalyst at 40 C., under 5?105 Pa pressure for 2 to 3 hours. After taking up the hydrogen, the catalyst is filtered and the filtrate is evaporated to solvent-free. The evaporation residue (weighing 6.6 g) is dissolved in 80 ml of methanol, a solution of 3 g (0.02 mol) of (+)-D-tartaric acid in 20 ml of methanol is added at room temperature and the mixture is stirred for 5 hours. The precipitated crystalline product is filtered to yield 3.2 g (66%) of (?)-trans-4-(4-flurophenyl)-3-(3,4-metylenedioxyphenoxymethyl)piperidine (+)-D-tartarate, m.p.: 178-180 C.; [?]D20?50.5 (c=1, dimethylformamide). The above salt is stirred at 40 C. with a solution of 1.1 g of ammonium chloride in 25 ml of water for 2 hours, then the crystalline precipitate is filtered at 10 C., washed with cold water and dried on the air to give 2.1 g (85%) of title compound, m.p.: 136-138 C.; . [?]D20 ?86,4 (c=1, methanol The water content of the product is 2.45% (measured by Karl Fischers method).

Reference： [1]Current Patent Assignee: angolul : Chemical Works of Gedeon Richter Plc. Gedeon Richter Plc. - US6657062, 2003, B1 Location in patent: Page column 13

33
[ 391677-98-8 ]
[ 147-71-7 ]
(2R)-amino-2-methyl-4-thiophen-2-ylbutan-1-ol 1/2D-(-)-tartrate [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
99.7%	Stage #1: (4R)-4-methyl-4-[2-(thiophen-2-yl)ethyl]-1,3-oxazolidin-2-one With potassium hydroxide In tetrahydrofuran; methanol; dichloromethane at 80℃; for 48h; Stage #2: D-tartaric acid In ethanol	47.a EXAMPLE 47(a) (2R)-Amino-2-methyl-4-thiophen-2-ylbutan-1-ol 1/2D-(?)-tartrate (2R)-Amino-2-methyl-4-thiophen-2-ylbutan-1-ol 1/2D-(-)-tartrate [1075] (4R)-Methyl-4-[2-(thiophen-2-yl)]ethyloxazolidin-2-one (85% ee, 7.30 g, 34.6 mmol) obtained in Example 56 was dissolved in the mixture of tetrahydrofuran (35 ml) and methanol (70 ml), and a 5N aqueous potassium hydroxide solution (70 ml) was added thereto in an ice bath followed by stirring for 2 days at 80° C. To the reaction solution was added dichloromethane, and the solution was washed with water. The dichloromethane layer was dried over anhydrous magnesium sulfate, and the solvent was evaporated under reduced pressure. The obtained residue (6.20 g) was dissolved in ethanol (60 ml), and D-(-)-tartaric acid (5.19 g, 34.6 mmol) in ethanol (50 ml) was added thereto to give a precipitate. The precipitate was filtered off to afford the crude title compound (7.56 g). The obtained crude target compound (7.54 g) was recrystallized from a mixture of ethanol (75 ml) and water (50 ml), and the title compound (5.89 g, 98% ee) was obtained. In addition, the obtained target compound (5.88 g) was recrystallized from ethanol (60 ml) and water (54 ml) to afford the title compound (5.11 g, 99.7% ee). [1076] Infrared absorption spectrum νmax cm-1 (KBr): 3400, 3218, 3126, 2937, 2596, 1599, 1530, 1400, 1124, 1077,715 [1077] Anal. Calcd.(%) for C9H15NOS.0.5C4H4O6: C, 50.95; H, 6.61; N, 5.40; S, 12.36 [1078] Found: C, 50.68; H, 6.91; N, 5.38; S, 12.48 [1079] [α]D24-14 (c 1.00, H2O)

Reference： [1]Current Patent Assignee: DAIICHI SANKYO COMPANY, LIMITED - US2003/236297, 2003, A1 Location in patent: Page 103

34
[ 147-71-7 ]
[ 20439-47-8 ]
[ 116407-32-0 ]

Yield	Reaction Conditions	Operation in experiment
97%	In tetrahydrofuran for 36h; Reflux;
55.8%	Stage #1: D-tartaric acid; (1R,2R)-1,2-diaminocyclohexane In water at 25 - 90℃; Stage #2: With acetic acid In water at 85 - 90℃; for 2h;	1 Embodiment 1 A method for preparing trans-cyclohexanediamine tartrate comprises the following steps: (1) FeedingAdding 112.0 kg of D-tartaric acid, 400 kg of deionized water to the reaction vessel, and stirring to 25 ° C with heating;The D-tartaric acid has a purity of ≥99%.(2) dropwise addition of transcyclohexanediamineWhen the temperature is raised to 25 ° C, the liquid in the reaction kettle is a light yellow transparent liquid, and the transcyclohexanediamine is started to be added dropwise;The amount of addition was 190.0 kg, and the dropping time was 1 hour;This process is an exothermic reaction. As the temperature of the instillation reaction of cyclohexanediamine increases, white crystals precipitate, up to about 70 °C.After the addition of cyclohexanediamine,Generally crystals will dissolve, otherwiseSlightly heated to dissolve, but this process needs to control the dissolution temperature can not exceed 90 ° C;The trans-cyclohexanediamine has a trans content of 70%. (3) Add glacial acetic acid dropwiseAfter the addition of the transcyclohexanediamine was completed, and the crystals were all dissolved, glacial acetic acid was added dropwise, and the amount of the dropwise addition was 93.0 kg.With the instillation of glacial acetic acid, a large amount of white crystals were precipitated, and glacial acetic acid was controlled for 30-45 minutes; the temperature was dropped.Not more than 85 ° C;The glacial acetic acid has a purity of 99%.(4) Insulation reactionIncubate at 85 to 90 ° C for 2 hours.(5) coolingSlowly slowly cool to 12 ° C for at least 4 hours and stir for another half an hour at 12 ° C;If the heat is directly reacted, the cooling of the ice water will have an adverse effect on product yield and low-temperature cooling crystallization.The glacial acetic acid has a purity of ≥99%.(6) rinsingCentrifugation to obtain off-white crystals, rinsed with 200 kg of water, then rinsed with 200 kg of methanol, and centrifuged to dryness;The methanol has a purity of ≥99%.(7) DryingThe obtained solid was dried at 70 ° C for 1 hour to obtain 110 kg of a trans-cyclohexanediamine tartrate product.The trans-cyclohexanediamine tartrate has a specific rotation of -11° to -13°; the content is ≥98.0%, and the appearance is white-like.Crystal.The yield of the finished product was calculated to be 55.8%; the reaction conditions were mild, the operation was simple, the pressure was carried out under normal pressure, and the safety was high.

Reference： [1]Velázquez, Daniel García; Díaz, David Díaz; Ravelo, Ángel Gutiérrez; Tellado, José Juan Marrero [Journal of the American Chemical Society, 2008, vol. 130, # 25, p. 7967 - 7973]
[2]Current Patent Assignee: WEIFANG HUITAO CHEMICAL - CN109336757, 2019, A Location in patent: Paragraph 0020-0030

35
[ 64271-00-7 ]
[ 147-71-7 ]
[ 780760-09-0 ]

Yield	Reaction Conditions	Operation in experiment
44.8%	With trifluoroacetic acid; In methanol; water; at 25 - 60℃; for 2h;Product distribution / selectivity;	To a solution of racemic amine (5.0 g, 35.9 mmole, prepared as described above) in methanol (25 mL) and water (1.8 mL) was added an acid (0.5 equiv., 18.0 mmole, see table below). The solution was warmed to 60 0C. A solution of D-tartaric acid (3.23 g, 21.6 mmole, 0.6 equiv.) in methanol (15 mL) was added dropwise over 10 min. The reaction was held at 60 0C for 20 <n="41"/>min., cooled to 25 0C over 90 minutes, and seeded with a small amount of product. After product precipitated the suspension was cooled to 0-10 0C over 30 minutes, held 30 minutes, then filtered under vacuum and washed with methanol (10 mL). The wet cake was dried in a vacuum oven for 12 hours to afford a white crystalline solid (see table below for yield).Acid Yield (%) Ee none 19.3 96.5 acetic acid 34.2 98.9 formic acid 39.1 97.3 malonic acid 44.7 98.5 hydrochloric acid 43.2 99.0 chloroacetic acid 44.9 98.4 trifluoroacetic acid 44.8 99.4
44.7%	With malonic acid; In methanol; water; at 25 - 60℃; for 2h;Product distribution / selectivity;	To a solution of racemic amine (5.0 g, 35.9 mmole, prepared as described above) in methanol (25 mL) and water (1.8 mL) was added an acid (0.5 equiv., 18.0 mmole, see table below). The solution was warmed to 60 0C. A solution of D-tartaric acid (3.23 g, 21.6 mmole, 0.6 equiv.) in methanol (15 mL) was added dropwise over 10 min. The reaction was held at 60 0C for 20 <n="41"/>min., cooled to 25 0C over 90 minutes, and seeded with a small amount of product. After product precipitated the suspension was cooled to 0-10 0C over 30 minutes, held 30 minutes, then filtered under vacuum and washed with methanol (10 mL). The wet cake was dried in a vacuum oven for 12 hours to afford a white crystalline solid (see table below for yield).Acid Yield (%) Ee none 19.3 96.5 acetic acid 34.2 98.9 formic acid 39.1 97.3 malonic acid 44.7 98.5 hydrochloric acid 43.2 99.0 chloroacetic acid 44.9 98.4 trifluoroacetic acid 44.8 99.4
44.9%	With chloroacetic acid; In methanol; water; at 25 - 60℃; for 2h;Product distribution / selectivity;	To a solution of racemic amine (5.0 g, 35.9 mmole, prepared as described above) in methanol (25 mL) and water (1.8 mL) was added an acid (0.5 equiv., 18.0 mmole, see table below). The solution was warmed to 60 0C. A solution of D-tartaric acid (3.23 g, 21.6 mmole, 0.6 equiv.) in methanol (15 mL) was added dropwise over 10 min. The reaction was held at 60 0C for 20 <n="41"/>min., cooled to 25 0C over 90 minutes, and seeded with a small amount of product. After product precipitated the suspension was cooled to 0-10 0C over 30 minutes, held 30 minutes, then filtered under vacuum and washed with methanol (10 mL). The wet cake was dried in a vacuum oven for 12 hours to afford a white crystalline solid (see table below for yield).Acid Yield (%) Ee none 19.3 96.5 acetic acid 34.2 98.9 formic acid 39.1 97.3 malonic acid 44.7 98.5 hydrochloric acid 43.2 99.0 chloroacetic acid 44.9 98.4 trifluoroacetic acid 44.8 99.4

43.2%	With hydrogenchloride; In methanol; water; at 25 - 60℃; for 2h;Product distribution / selectivity;	To a solution of racemic amine (5.0 g, 35.9 mmole, prepared as described above) in methanol (25 mL) and water (1.8 mL) was added an acid (0.5 equiv., 18.0 mmole, see table below). The solution was warmed to 60 0C. A solution of D-tartaric acid (3.23 g, 21.6 mmole, 0.6 equiv.) in methanol (15 mL) was added dropwise over 10 min. The reaction was held at 60 0C for 20 <n="41"/>min., cooled to 25 0C over 90 minutes, and seeded with a small amount of product. After product precipitated the suspension was cooled to 0-10 0C over 30 minutes, held 30 minutes, then filtered under vacuum and washed with methanol (10 mL). The wet cake was dried in a vacuum oven for 12 hours to afford a white crystalline solid (see table below for yield).Acid Yield (%) Ee none 19.3 96.5 acetic acid 34.2 98.9 formic acid 39.1 97.3 malonic acid 44.7 98.5 hydrochloric acid 43.2 99.0 chloroacetic acid 44.9 98.4 trifluoroacetic acid 44.8 99.4
42.3%	In methanol; at 0 - 50℃; for 2.83h;Product distribution / selectivity;	To a stirred solution of 60 g 2-methyl-5-propionylfuran (1.0 equiv., 0.434 mol) and 69 mL formamide (1.74 mol, 4.0 equiv.) at 25 0C was added 16.4 mL formic acid (0.434 mol, 1.0 equiv.). The resulting solution was heated to 140-150 0C over 1 hour, held at this temperature for 16 hours, and then cooled to 20-30 0C over 1 hour. To the stirred solution of crude intermediate amide product was added 377 mL 25% w/w aq. NaOH (2.89 mol NaOH1 7.0 <n="40"/>equiv.). The heterogeneous solution was vigorously agitated to achieve a homogeneous mixture. The solution was heated to 80-90 0C over 30 min., held at this temperature for 6 hours, then cooled to 20-30 0C over 1 hour. The phases were allowed to separate, and the aqueous layer was drained. The crude racemic amine was distilled under vacuum (20-25 mmHg) to afford 50.1 g (82% yield) of a pale yellow oil; bp = 60-65 0C (40-45 mmHg); 1H NMR (DMSO-D6): delta 0.84 (3H, t, J = 7.4 Hz), 1.49-1.58 (1H, m), 1.61-1.71 (1H, m), 1.61 (2H, brs), 2.21 (3H, s), 3.63 (1H, t, J = 6.54 Hz), 5.93 (1H, dd, J = 2.98, 1.00 Hz), 6.00 (1H, d, J = 1.0 Hz); 13C NMR (DMSO-D6): 10.6, 13.6, 29.7, 51.1, 105.2, 106.1, 149.8, 158.5 ppm. To a solution of the racemic amine in 250 mL methanol was added 50.5 g D-tartaric acid (336.5 mmole) as a solution in 150 mL methanol over 30 minutes. The solution was heated to 40- 50 0C and held at this temperature for 20 minutes. The reaction was slowly cooled to 0-10 0C over 2 hours. The suspension was then filtered under vacuum and washed with methanol (100 mL). The wet cake was dried in a vacuum oven at 50-60 0C for at least 8 hours to afford 44.1 g (42.3% yield from racemic amine, 94% ee) of a white crystalline solid; characterized as above.
39.1%	With formic acid; In methanol; water; at 25 - 60℃; for 2h;Product distribution / selectivity;	To a solution of racemic amine (5.0 g, 35.9 mmole, prepared as described above) in methanol (25 mL) and water (1.8 mL) was added an acid (0.5 equiv., 18.0 mmole, see table below). The solution was warmed to 60 0C. A solution of D-tartaric acid (3.23 g, 21.6 mmole, 0.6 equiv.) in methanol (15 mL) was added dropwise over 10 min. The reaction was held at 60 0C for 20 <n="41"/>min., cooled to 25 0C over 90 minutes, and seeded with a small amount of product. After product precipitated the suspension was cooled to 0-10 0C over 30 minutes, held 30 minutes, then filtered under vacuum and washed with methanol (10 mL). The wet cake was dried in a vacuum oven for 12 hours to afford a white crystalline solid (see table below for yield).Acid Yield (%) Ee none 19.3 96.5 acetic acid 34.2 98.9 formic acid 39.1 97.3 malonic acid 44.7 98.5 hydrochloric acid 43.2 99.0 chloroacetic acid 44.9 98.4 trifluoroacetic acid 44.8 99.4
34.2%	With acetic acid; In methanol; water; at 25 - 60℃; for 2h;Product distribution / selectivity;	To a solution of racemic amine (5.0 g, 35.9 mmole, prepared as described above) in methanol (25 mL) and water (1.8 mL) was added an acid (0.5 equiv., 18.0 mmole, see table below). The solution was warmed to 60 0C. A solution of D-tartaric acid (3.23 g, 21.6 mmole, 0.6 equiv.) in methanol (15 mL) was added dropwise over 10 min. The reaction was held at 60 0C for 20 <n="41"/>min., cooled to 25 0C over 90 minutes, and seeded with a small amount of product. After product precipitated the suspension was cooled to 0-10 0C over 30 minutes, held 30 minutes, then filtered under vacuum and washed with methanol (10 mL). The wet cake was dried in a vacuum oven for 12 hours to afford a white crystalline solid (see table below for yield).Acid Yield (%) Ee none 19.3 96.5 acetic acid 34.2 98.9 formic acid 39.1 97.3 malonic acid 44.7 98.5 hydrochloric acid 43.2 99.0 chloroacetic acid 44.9 98.4 trifluoroacetic acid 44.8 99.4
19.3%	In methanol; water; at 15 - 60℃; for 2 - 2.75h;Product distribution / selectivity;	To a stirred solution of 100 g 2-methyl-5-propionylfuran (1.0 equiv., 0.724 mol) and 115 mL formamide (2.90 mol, 4.0 equiv.) at 25 0C was added 30.0 mL formic acid (0.796 mol, 1.1 equiv.). A small exotherm was observed. The resulting solution was heated to 140-150 0C over 1 hour, held at this temperature for 12 hours, and then cooled to 20-30 0C over 1 hour. To the stirred solution of crude intermediate amide product was added 641 mL 25% w/w aq. NaOH (5.07 mol NaOH, 7.0 equiv.). An exotherm was observed. The heterogeneous solution was vigorously agitated to achieve a homogeneous mixture. The solution was heated to 65-70 0C over 30 min., held at this temperature for 10 hours, then cooled to 20-30 0C over 1 hour. The phases were allowed to separate, drained the aqueous layer, then washed the <n="39"/>organic layer of crude racemic amine twice with 10% aq. NaCI (100 ml_). The crude racemic amine was taken up in 350 mL methanol and 28 mL water. The solution was heated to 50-60 0C and to it was added 73.5 g D-tartaric acid (0.502 mol, 1.0 equiv.) as a solution in 210 mL methanol and 14 mL water over 30 minutes. The reaction was held at 60 0C for 15 min, then cooled to 15-35 0C over 2 hours. The suspension was then filtered under vacuum and washed twice with 70 mL methanol. The wet cake was dried in a vacuum oven at 50-60 0C for at least 8 hours to afford 60.1 g (28.7% yield, 99% ee) of a white crystalline solid; mp = 191-1940C; 1H NMR (DMSO-D6): delta 0.81 (t, 3H, J=7.4 Hz), 1.79-1.95 (m, 2H), 2.26 (s, 3H), 3.99 (s, 2H), 4.18 (dd, 1H, J=8.9, 5.7 Hz)1 6.07 (dd, 1H, J=3.1, 1.1 Hz), 6.38 (d, 1H, J=3.1 Hz), and 8.16 (brs, 6H). 13C NMR (DMSO-D6): 10.31, 13.63, 25.46, 49.40, 72.31, 107.03, 109.98, 149.46, 152.01, 175.01 ppm.EXAMPLE IVa - Preparation Using a Coacid in Resolution of tartarate salt of alpha-(R)-Ethyl-5-methyl-2-furanmethanamine D-tartrate (2DaDTo a solution of racemic amine (5.0 g, 35.9 mmole, prepared as described above) in methanol (25 mL) and water (1.8 mL) was added an acid (0.5 equiv., 18.0 mmole, see table below). The solution was warmed to 60 0C. A solution of D-tartaric acid (3.23 g, 21.6 mmole, 0.6 equiv.) in methanol (15 mL) was added dropwise over 10 min. The reaction was held at 60 0C for 20 <n="41"/>min., cooled to 25 0C over 90 minutes, and seeded with a small amount of product. After product precipitated the suspension was cooled to 0-10 0C over 30 minutes, held 30 minutes, then filtered under vacuum and washed with methanol (10 mL). The wet cake was dried in a vacuum oven for 12 hours to afford a white crystalline solid (see table below for yield).Acid Yield (%) Ee none 19.3 96.5 acetic acid 34.2 98.9 formic acid 39.1 97.3 malonic acid 44.7 98.5 hydrochloric acid 43.2 99.0 chloroacetic acid 44.9 98.4 trifluoroacetic acid 44.8 99.4

Reference： [1]Patent: WO2009/5801,2009,A1 .Location in patent: Page/Page column 39-40
[2]Patent: WO2009/5801,2009,A1 .Location in patent: Page/Page column 39-40
[3]Patent: WO2009/5801,2009,A1 .Location in patent: Page/Page column 39-40
[4]Patent: WO2009/5801,2009,A1 .Location in patent: Page/Page column 39-40
[5]Patent: WO2009/5801,2009,A1 .Location in patent: Page/Page column 38-39
[6]Patent: WO2009/5801,2009,A1 .Location in patent: Page/Page column 39-40
[7]Patent: WO2009/5801,2009,A1 .Location in patent: Page/Page column 39-40
[8]Patent: WO2009/5801,2009,A1 .Location in patent: Page/Page column 37-40

36
[ 100125-12-0 ]
cadmium(II) nitrate hexahydrate [ No CAS ]
[ 147-71-7 ]
[Cd(3,8-dibromo-1,10-phenanthroline-κ2-N,N')(L-tartaric acid(-2H))](n) [ No CAS ]

Reference： [1]Journal of Molecular Structure,2009,vol. 920,p. 270 - 276

37
[ 147-71-7 ]
[ 872-73-1 ]
1,2-dimethylpyridinium (D)-tartrate [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
96%	With silver hydroxide In water for 24h;

Reference： [1]Zhang, Suling; Huang, Yongzhong; Jing, Huanwang; Yao, Weixuan; Yan, Peng [Green Chemistry, 2009, vol. 11, # 7, p. 935 - 938]

38
[ 147-71-7 ]
[ 22990-19-8 ]
(1S)-1-phenyl-1,2,3,4-tetrahydroisoquinoline (D)-(-)-tartrate [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
	In methanol; at 24℃;Reflux;Product distribution / selectivity;	Racemic mixture of 1 -phenyl- 1, 2,3, 4-tetrahydroisoquinoline (40 g, 191 mmol) and D-(-)-tartaric acid (28.61 g, 191 mmol, ee 99%) are suspended in methanol (240 niL). The solution is heated to reflux, until the whole amount of solid is completely dissolved. The heating bath is being removed and to the clear solution water (120 mL) is added; the resulting mixture is left at ambient temperature (240C) for 24 h. Crystalline solid is filtered off (21.45 g). -17.02 (c=l%, H2O).Obtained crystalline solid is suspended in the mixture of 10% NaOHaq (120 mL) and ethyl acetate (50 mL), the solution is stirred at ambient temperature (240C) for about 10 min. until the whole amount of solid is dissolved. The reaction mixture is transferred into separatory flask, organic layer is separated and water phase is extracted with ethyl acetate (2x30 mL). Combined organic extracts are washed with water (1x40 mL), dried and condensed under vacuum to dryness. (S)-1-Phenyl- 1,2,3, 4-tetrahydroisoquinoline is obtained as crystalline solid (12 g, 30%), of enantiomeric excess ee = 100%. Chemical purity (HPLC): 99.96%; [alpha]25D = 38.20 (c=l%, CH2Cl2).

Reference： [1]Patent: WO2009/142521,2009,A1 .Location in patent: Page/Page column 6

39
[ 147-71-7 ]
[ 111470-99-6 ]
S(-) amlodipine hemi D(-) tartarate [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
		1. N, N-Dimethylacetamide (DMAC) (152.7 kg) was charged to a 100 gal reactor (T-110A). 2. D-Tartaric acid (13.88 kg) was charged slowly to T-110A. 3. The solution in T-110A was mixed and held for use later in the batch. 4. (RS)-<strong>[111470-99-6]Amlodipine besylate</strong> (49.81kg) was charged to a 200 gal reactor (R-120), followed by methyl t-butyl ether (MTBE) (239.3 kg). 5. Aqueous sodium hydroxide (1 N) (137.2 kg) was added to R-120. 6. The contents of R-120 were agitated for 20-30 minutes and then the layers were allowed to separate for a minimum of 15 minutes. 7. The bottom aqueous layer was removed and USP water (66.0 kg) was charged to R-120. 8. The contents of R-120 were agitated for a minimum of 20 minutes and then the layers were allowed to separate for a minimum of 15 minutes. 9. The bottom aqueous layer was removed and USP water (66.0 kg) was charged to R-120. 10. The contents of R-120 were agitated for a minimum of 20 minutes and then the layers were allowed to separate for a minimum of 15 minutes. 11. The bottom aqueous layer was removed from R-120. 12. The contents of R-120 were polish filtered through a 3 mum cartridge filter to R- 110A, followed by a reactor and line rinse with MTBE (49.9 kg). 13. The contents of R-110A were concentrated under vacuum (maximum 50C) to a calculated volume (109 L). 14. DMAC (152.8 kg) was charged to the contents of R-110A. 15. The contents of R-110A were again concentrated under vacuum, this time until the batch temperature reached 45-55C. The final volume was 208 L. 16. R-110A contents were cooled to 20 to 25C, followed by the addition of the previously prepared D-tartaric acid solution (166.0 kg) at 20-25C over 20 to 30 minutes. 17. The mixture was heated to 68-72C over 55 to 65 minutes, and held at this temperature for 55 to 65 minutes. 18. The reaction mixture was cooled to 21 to 23C over 2 to 3 hours using a linear cooling profile and agitated at this temperature for 30 to 40 minutes. 19. The slurry was filtered on a centrifuge (CE-102) in one load and washed with DMAC (75.7 kg) and MTBE (59.9 kg). 20. The wet cake was discharged (20.33 kg) and dried in vacuum tray dryer (D-401) for a minimum of 6 hours at 45-50C to yield 20.086 kg of (S(at)-Amlodipine Hemi-D-Tartrate DMAC solvate.

Reference： [1]Patent: WO2005/97191,2005,A2 .Location in patent: Page/Page column 94-95

40
[ 147-71-7 ]
[ 1007392-69-9 ]
(3'R,4'S)-6-[2-(2,6-dichloro-4-methyl-phenoxy)ethoxy]-1',2',3',4',5',6'-hexahydro-[3,4']bipyridinyl-3'-carboxylic acid [2-chloro-5-(2-methoxy-ethyl)benzyl]cyclopropylamide bis-D-tartrate [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
90%	In tetrahydrofuran at 20℃; for 20h;	11 Step 11 : Bis-D-tartrate salt Free base 12 (3.9 kg, 6.03 mol) dissolved in 30 L THF. D-taxtaric acid (1.809 kg, 12.06 mol) added neat and stirred at rt for 20 h. Tartaric acid slowly goes into solution and then salt slowly comes out. 45 L MTBE added over 1 h and stirred 1 h. Filtered, washing with 35 L 1.5:1 MTBE:THF. Dried under N2 flush to give 5.1 kg of bis-tartrate salt 14 (90%, 5.42 mol).
90%	In tetrahydrofuran at 20℃; for 20h; Large scale reaction;

Reference： [1]Current Patent Assignee: MERCK & CO INC - WO2010/11584, 2010, A2 Location in patent: Page/Page column 17-18
[2]Molinaro, Carmela; Shultz, Scott; Roy, Amélie; Lau, Stephen; Trinh, Thao; Angelaud, Rémy; O'Shea, Paul D.; Abele, Stefan; Cameron, Mark; Corley, Ed; Funel, Jacques-Alexis; Steinhuebel, Dietrich; Weisel, Mark; Krska, Shane [Journal of Organic Chemistry, 2011, vol. 76, # 4, p. 1062 - 1071]

41
[ 147-71-7 ]
[ 85650-52-8 ]
R-mirtazapine, D-tartaric acid salt [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
	In methanol; at 50℃;	Example 2 After combining 15.0 g (56.5 mmol, racemic mixture) of mirtazapine, 8.65 g (57.6 mmol) of D-tartaric acid and 180 mL of methanol, the obtained mixture was heated to 50C and stirred to obtain a homogeneous solution. Upon adding 18 mL of water dropwise thereto at the same temperature over a period of about 105 minutes, crystals were deposited. The obtained mixture was cooled to 25C over a period of about 15 hours. The crystals were separated from the obtained mixture by filtration, washed with 25 mL of methanol-water (10: 1) and then dried under reduced pressure to obtain 12.8 g of crude crystals of the D-tartaric acid salt of R-mirtazapine as a white powder. The optical purity of the R-mirtazapine in the obtained crude crystals was 97.4% ee. After mixing 12.8 g of the crude crystals with 60 mL of methanol, the mixture was heated to 50C and mixed, causing complete dissolution of the crystals. Upon adding 6 mL of water thereto and mixing, crystals were deposited. The obtained mixture was cooled to 25C over a period of about 21 hours. The crystals were separated from the obtained mixture by filtration, washed with 5 mL of methanol-water (10:1) and then dried under reduced pressure to obtain 10.7 g of crude crystals of the D-tartaric acid salt of R-mirtazapine as a white powder. The optical purity of the R-mirtazapine in the obtained crystals was 100% ee. The water content of the crystals was 9.2 wt% as measured by the Karl Fischer method. Fig. 6 shows the 1H-NMR spectrum chart for the D-tartaric acid salt of R-mirtazapine.

Reference： [1]Patent: EP2174940,2010,A1 .Location in patent: Page/Page column 5

42
[ 147-71-7 ]
[ 1221443-65-7 ]
(R)-2,2-diethyl-8-(trifluoromethoxy)chroman-4-amine D-tartrate [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
	Stage #1: (R)-4-azido-8-trifluoromethoxy-2,2-diethylchroman In methanol at 50℃; for 3h; Stage #2: D-tartaric acid In methanol at 20℃; for 0.25h; Stage #3: In methanol; tert-butyl methyl ether at 0 - 20℃; for 1h;	55.55E A solution of methyl te/t-butylether (65 mL), (i?)-diphenyl(pyrrolidin-2-yl)methanol (279 mg, 1.01 mmol), and borane-iV,jV-diethylaniline complex (4.70 mL, 26.4 mmol) was heated to 45 0C. Example 55D (6.35 g, 22.0 mmol) in methyl tert-butylether (60 mL) was added over a 60 min period via addition funnel. The reaction was stirred an additional 15 min at 45 0C; LCMS analysis showed complete reaction. The reaction mixture was cooled to 5 0C and treated with MeOH (100 mL) was added keeping the temperature <10 0C (H2 evolution). The reaction was warmed to ambient temperature and stirred for 30 min. The reaction was diluted with MTBE (100 mL) and washed with 2 N HCl (2 x 50 mL) and brine (50 mL). The organic portion was dried (Na2SO4), filtered, and concentrated and the resulting residue (6.22 g) was used without further purification.To a solution of the crude (5)-2,2-diethyl-8-(trifluoromethoxy)chroman-4-ol (6.22 g, 21.4 mmol) described above in THF (50 mL) was added N,N-diisopropyethlyamine (7.79 mL, 45.0 mmol). The resulting yellow solution was cooled to -40 0C and solid methanesulfonic anhydride (8.59 g, 49.3 mmol) was added. The reaction mixture was warmed to -30 0C and stirred for 1 h. Tetrabutylammonium azide (14.6 g, 51.4 mmol) was added as a solid at -3O0C and the reaction was allowed to warm slowly to ambient temperature. MeOH (10OmL) was added followed by 2N NaOH (30 mL) and the reaction was stirred for 30 min. The reaction was diluted with MTBE (100 mL) and washed with 2N NaOH (30 mL), water (30 mL), 2N HCl (2 x 30 mL), and water (30 mL). The organic portion was dried (Na2SO4), filtered, and concentrated to give an oily residue (6.80 g) that was used without further purification.The crude (i?)-4-azido-8-trifluoromethoxy-2,2-diethylchroman described above was dissolved in MeOH (70 mL) and placed in a 250 mL stainless steel pressure bottle. 5% Pd-C (650 mg) was added and the reaction mixture was stirred for 3 h at 50 0C and 30 psi. Upon cooling, the reaction mixture was filtered through a nylon membrane and concentrated to give an oily residue (6.10 g) that was used without further purification.The crude (i?)-2,2-diethyl-8-(trifluoromethoxy)chroman-4-amine (6.10 g, 21.1 mmol) described above was dissolved in MeOH (60 mL), stirred rapidly at ambient temperature, and treated with D-(-)-tartaric acid (3.16 g, 21.1 mmol). After 15 min, MTBE (60 mL) was added and after 20 minutes a solid began to form. The reaction was stirred for another 20 min then cooled to 0 0C and stirred for 20 min. The resulting solid was collected by filtration, washed with MTBE (30 mL), and dried in vacuum oven for 8 h to provide the title compound (4.82 g, 11.0 mmol, 52% from Example 52D) as a white solid. MS (DCI/NH3) m/z 290 (M+H)+.
	Stage #1: (R)-4-azido-8-trifluoromethoxy-2,2-diethylchroman In methanol at 50℃; for 3h; Stage #2: D-tartaric acid In methanol at 20℃; for 0.25h; Stage #3: In methanol; tert-butyl methyl ether at 0 - 20℃; for 1h;	55.55E A solution of methyl te/t-butylether (65 mL), (i?)-diphenyl(pyrrolidin-2-yl)methanol (279 mg, 1.01 mmol), and borane-iV,jV-diethylaniline complex (4.70 mL, 26.4 mmol) was heated to 45 0C. Example 55D (6.35 g, 22.0 mmol) in methyl tert-butylether (60 mL) was added over a 60 min period via addition funnel. The reaction was stirred an additional 15 min at 45 0C; LCMS analysis showed complete reaction. The reaction mixture was cooled to 5 0C and treated with MeOH (100 mL) was added keeping the temperature <10 0C (H2 evolution). The reaction was warmed to ambient temperature and stirred for 30 min. The reaction was diluted with MTBE (100 mL) and washed with 2 N HCl (2 x 50 mL) and brine (50 mL). The organic portion was dried (Na2SO4), filtered, and concentrated and the resulting residue (6.22 g) was used without further purification.To a solution of the crude (5)-2,2-diethyl-8-(trifluoromethoxy)chroman-4-ol (6.22 g, 21.4 mmol) described above in THF (50 mL) was added N,N-diisopropyethlyamine (7.79 mL, 45.0 mmol). The resulting yellow solution was cooled to -40 0C and solid methanesulfonic anhydride (8.59 g, 49.3 mmol) was added. The reaction mixture was warmed to -30 0C and stirred for 1 h. Tetrabutylammonium azide (14.6 g, 51.4 mmol) was added as a solid at -3O0C and the reaction was allowed to warm slowly to ambient temperature. MeOH (10OmL) was added followed by 2N NaOH (30 mL) and the reaction was stirred for 30 min. The reaction was diluted with MTBE (100 mL) and washed with 2N NaOH (30 mL), water (30 mL), 2N HCl (2 x 30 mL), and water (30 mL). The organic portion was dried (Na2SO4), filtered, and concentrated to give an oily residue (6.80 g) that was used without further purification.The crude (i?)-4-azido-8-trifluoromethoxy-2,2-diethylchroman described above was dissolved in MeOH (70 mL) and placed in a 250 mL stainless steel pressure bottle. 5% Pd-C (650 mg) was added and the reaction mixture was stirred for 3 h at 50 0C and 30 psi. Upon cooling, the reaction mixture was filtered through a nylon membrane and concentrated to give an oily residue (6.10 g) that was used without further purification.The crude (i?)-2,2-diethyl-8-(trifluoromethoxy)chroman-4-amine (6.10 g, 21.1 mmol) described above was dissolved in MeOH (60 mL), stirred rapidly at ambient temperature, and treated with D-(-)-tartaric acid (3.16 g, 21.1 mmol). After 15 min, MTBE (60 mL) was added and after 20 minutes a solid began to form. The reaction was stirred for another 20 min then cooled to 0 0C and stirred for 20 min. The resulting solid was collected by filtration, washed with MTBE (30 mL), and dried in vacuum oven for 8 h to provide the title compound (4.82 g, 11.0 mmol, 52% from Example 52D) as a white solid. MS (DCI/NH3) m/z 290 (M+H)+.

Reference： [1]Current Patent Assignee: ABBVIE INC - WO2010/45401, 2010, A1 Location in patent: Page/Page column 71-73
[2]Current Patent Assignee: ABBVIE INC - WO2010/45402, 2010, A1 Location in patent: Page/Page column 70-71

43
[ 147-71-7 ]
C₁₅H₂₀ClF₂NO₂S [ No CAS ]
[ 1221445-11-9 ]

Yield	Reaction Conditions	Operation in experiment
76%	Stage #1: C₁₅H₂₀ClF₂NO₂S With methanol; acetyl chloride In tert-butyl methyl ether at 5℃; for 0.166667h; Stage #2: D-tartaric acid In isopropyl alcohol at 70℃; for 0.5h;	124.124C A yellow slurry of Example 124B (13.97 g, 39.70 mmol) in MTBE (140 mL) was stirred at ambient temperature and HCl in methanol, formed from addition of acetyl chloride (5.65 mL, 79.0 mmol) to methanol (14.5 mL, 357 mmol) at <5 0C, was added. After 10 min, the reaction mixture was filtered; the precipitate was collected and washed with 10% MeOH/MTBE (2 x 10 niL). The resulting off-white solid was dried in a vacuum oven at 60 0C to and was used without subsequent purification.D-(-)-Tartaric acid (5.33 g, 35.5 mmol) and isopropanol (90 mL) heated to 70 0C, and a solution of crude (4i?)-7-chloro-2-(difluoromethyl)-2-methylchroman-4-amine (8.80 g, 35.5 mmol) from above in isopropanol (45 mL) was added over 30 min. The reaction mixture was cooled to ambient temperature and the precipitate collected by filtration, washed with isopropanol, and dried in a vacuum oven at 60 0C for 6 hours to give the title compound (10.7 g, 26.9 mmol, 76% yield). MS (DCI/NH3) m/z 248 (M+NH4-H2O)+.
76%	Stage #1: C₁₅H₂₀ClF₂NO₂S With methanol; acetyl chloride In tert-butyl methyl ether at 5℃; for 0.166667h; Stage #2: D-tartaric acid In isopropyl alcohol at 70℃; for 0.5h;	124.124C A yellow slurry of Example 124B (13.97 g, 39.70 mmol) in MTBE (140 mL) was stirred at ambient temperature and HCl in methanol, formed from addition of acetyl chloride (5.65 mL, 79.0 mmol) to methanol (14.5 mL, 357 mmol) at <5 0C, was added. After 10 min, the reaction mixture was filtered; the precipitate was collected and washed with 10% MeOH/MTBE (2 x 10 niL). The resulting off-white solid was dried in a vacuum oven at 60 0C to and was used without subsequent purification.D-(-)-Tartaric acid (5.33 g, 35.5 mmol) and isopropanol (90 mL) heated to 70 0C, and a solution of crude (4i?)-7-chloro-2-(difluoromethyl)-2-methylchroman-4-amine (8.80 g, 35.5 mmol) from above in isopropanol (45 mL) was added over 30 min. The reaction mixture was cooled to ambient temperature and the precipitate collected by filtration, washed with isopropanol, and dried in a vacuum oven at 60 0C for 6 hours to give the title compound (10.7 g, 26.9 mmol, 76% yield). MS (DCI/NH3) m/z 248 (M+NH4-H2O)+.

Reference： [1]Current Patent Assignee: ABBVIE INC - WO2010/45401, 2010, A1 Location in patent: Page/Page column 124-125
[2]Current Patent Assignee: ABBVIE INC - WO2010/45402, 2010, A1 Location in patent: Page/Page column 123

44
[ 147-71-7 ]
lasofoxifene [ No CAS ]
[ 190791-29-8 ]

Yield	Reaction Conditions	Operation in experiment
50.3%	In ethanol; for 0.08333330000000001h;Reflux;	The racemic base 2b, prepared in Example 3, optionally purified as described in Example 4, 5 or 6, in the quantity of 17.2 g is dissolved in 172 ml of warm wine spirit. A solution of 6.24 g of D-tartaric acid in 62 ml of wine spirit is added to this solution and the resulting solution is carefully heated to slight reflux for 5 minutes. During spontaneous cooling the required lasofoxifene D-tartrate precipitates in the yield of 11.8 g, i.e. 50.3percent.

Reference： [1]Patent: US2010/256394,2010,A1 .Location in patent: Page/Page column 8

45
[ 147-71-7 ]
[ 87-69-4 ]
[ 88150-42-9 ]
(R)-amlodipine-D-hemitartrate [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
67.7%		Example 14Preparation of (R)-<strong>[88150-42-9]Amlodipine</strong>-D-hemitartrate DMF solvate.D-tartaric acid (1.47gms; 0.01 moles) was added to the mother liquor obtained fromExample 1. and stirred at ambient temperature for 240-300 minutes, till complete precipitation of the product. The title compound was then filtered and dried.Yield: 6.4 gms.%Yield; 67.7%.

Reference： [1]Patent: WO2006/43148,2006,A1 .Location in patent: Page/Page column 19

46
[ 147-71-7 ]
[ 104617-86-9 ]
[ 104632-28-2 ]
[ 104632-26-0 ]

Yield	Reaction Conditions	Operation in experiment
		(00260] EXAMPLE 15 - Industrial scale resolution of racemic diamine:; A 72 L, unjacketed reactor was charged with racemic 2,6 diamino-4,5,6,7-tetrahydro-benzothiazo.e (rac- diamine) (4.5 kg; 26.6 mol) and 58.5 L water, and heated as a suspension to a temperature of about 6OºC to 65ºC. Resolution of the enantiomers was achieved by addition of one equivalent of (D)-(-)-Tartaric acid (3991 grams; 26.6 mol) in 4.5 L of water, after which the resulting solution was heated to a temperature of about 7OºC to 75C and maintained at this temperature for about 1 hour. The mixture was allowed to cool to a temperature of about 2OºC to 25ºC and stirred for an additional 15 hours, after which the mixture was filtered and the solids were washed 3 X with water (6.3 L each wash).[00261] The wet solids, which contain the R(+) enantiomer of the diamine, were charged to the reactor followed by 54 L of water, and the mixture was heated to a temperature of about 7OºC to 75ºC for 2 hours. The mixture was allowed to cool to a temperature of about 2OºC to 25ºC and stirred for 17 hours. The mixture was then filtered and the solids were washed 2 X with water (4.5 L each wash). The wet solids were transferred to a jacketed reactor and the reactor was charged with 8.1 L of water. The mixture was cooled to a temperature of about OºC to 5ºC and cautiously charged with concentrated 1.625 L of HCl, followed by 1.155 L of 50% NaOH to achieve a pH of about 9-10. During the addition the temperature was maintained at about OºC to 5ºC, and stirred for an additional hour at temperature. The resulting mixture was then filtered and the solids were washed 2 X with cold (OºC to 5C) water (1.125 L each wash). The solids were transferred to a jacketed reactor and were reslurried once more with 4.5 L of water at OºC to 5ºC. The solids were filtered and dried under warm air (4OºC to 45ºC) to give 1940 grams of the product (R(+) diamine) as a white solid, with an 86% yield for the R(+) enantiomer. [00262] The mother liquors of the initial resolution step, which contain the S(-) enantiomer of the diamine, were concentrated to afford diamine with a 95.5% yield for the S(-) enantiomer.

Reference： [1]Patent: WO2010/22140,2010,A1 .Location in patent: Page/Page column 100-101

47
[ 147-71-7 ]
[ 112984-60-8 ]
[ 1189344-09-9 ]

Yield	Reaction Conditions	Operation in experiment
	In dimethyl sulfoxide; at 20℃; for 20h;	Example 1; Preparation of (S)-6-fluoro-1-methyl-4-oxo-7-(1-piperazinyl)-1H,4H-[1,3]thiazeto[3,2-a]quinoline-3-carboxylic acid; Racemic <strong>[112984-60-8]ulifloxacin</strong> (105 g) was dissolved in DMSO (1500 mL). D-tartrate (27 g) solution in DMSO (405 mL) was added to the racemic ulifoxacin solution with agitation. Cloudiness and precipitation appeared. After 20 hours of agitation at an ambient temperature, the mixture was filtered. The solid was dried under vacuum to yield 86 g of solid. The solid was recrystallized in DMSO to yield 37 g of (S)-6-fluoro-1-methyl-4-oxo-7-(1-piperazinyl)-1H,4H-[1,3]thiazeto[3,2-a]quinoline-3-carboxylic acid-D-tartrate salt; elemental analysis indicated: C 49.08%, H 5.06%, N 9.50%, and S 7.44% (corresponding to: C16H16FN3O3S.1/2C4H6O6.H2O, calculated value: C 48.86%, H 4.78, N 9.50%, and S 7.25%). The salt was dispersed in water and the dispersion was neutralized with 2% NaOH aqueous solution to a pH value of 7 to 8. The precipitate was filtered and dried to yield 24.5 g of (S)-6-fluoro-1-methyl-4-oxo-7-(1-piperazinyl)-1H,4H-[1,3]thiazeto[3,2-a]quinoline-3-carboxylic acid. It had a rotation [alpha]D20=-143.4 (c=0.15, 0.1 mol/L NaOH), 1H-NMR (DMSO-d6) delta2.11 (3H, d, j=6.2 Hz), 2.85-3.20 (8H, m), 6.40 (1H, q, j=6.2 Hz), 6.89 (1H, d, j=7.4 Hz), 7.79 (1H, d, j=13.9 Hz), optical purity e.e.>95%.

Reference： [1]Patent: US2011/28444,2011,A1 .Location in patent: Page/Page column 2-3

48
[ 147-71-7 ]
[ 22990-19-8 ]
(1S)-1-phenyl-1,2,3,4-tetrahydroisoquinoline (D)-(-)-tartrate [ No CAS ]
(1R)-1-phenyl-1,2,3,4-tetrahydroisoquinoline (D)-(-)-tartrate [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
	In water;	Resolution of (R:S)-1 -phenyl- 1,2,3,4-tetrahydroisoquinoline (100 g) was carried out using (D)-(-)-tartaric acid in water as per the literature method known in the art (Ref 1.- J. Chem. Soc. Perkin. Trans I, (4), 869-73 (1988), Ref. 2.- Monatshefte Fur. Chemie, vol. 53-54:956-962(1929)) and diastereomeric (D)-(-)-tartaric acid salt of (1S)- 1 -phenyl- 1,2,3,4-tetrahydroisoquinoline was filtered out as a solid. The filtrate containing enantiomerically enriched (D)-(-)-tartaric acid salt of (lR)-l-phenyl-l,2,3,4- tetrahydroisoquinoline was collected and a clear aqueous solution 40 % aq. sodium hydroxide (NaOH, 85 mL) was added at room temperature when solid was precipitated. The precipitated solid was filtered and washed with water and dried. The weight of enantiomerically enriched (lR)-l-phenyl-l,2,3,4-tetrahydroisoquinoline was 61.0 g. (% Purity by HPLC-97.0 %; % Chiral purity of R-isomer -79.0 %).

Reference： [1]Patent: WO2011/48607,2011,A1 .Location in patent: Page/Page column 12

49
[ 147-71-7 ]
[ 2438-05-3 ]
C₄H₆O₆*2C₁₀H₁₂O₂ [ No CAS ]

Reference： [1]Molecular Crystals and Liquid Crystals,2010,vol. 528,p. 163 - 177

50
[ 147-71-7 ]
[ 3575-31-3 ]
C₄H₆O₆*2C₁₅H₂₂O₂ [ No CAS ]

Reference： [1]Molecular Crystals and Liquid Crystals,2010,vol. 528,p. 163 - 177

51
[ 147-71-7 ]
[ 173334-57-1 ]
(2S),(4S),(5S),(7S)-N-(3-amino-2,2-dimethyl-3-oxopropyl)-2,7-di(1-methylethyl)-4-hydroxy-5-amino-8-[4-methoxy-3-(3-methoxy-propoxy)phenyl]-octanamide hemi(D-tartrate) [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
	In water; for 0.5h;	Example 28<strong>[173334-57-1]Aliskiren</strong> D-Tartrate 2:1 A solution of 0.148 g (0.99 mmol) D-tartaric acid in 12 ml water was added to 1 .093 g (1.981 mmol) <strong>[173334-57-1]Aliskiren</strong> free base and stirred slowly for 30 min to obtain a turbid solution. By swirling the flask and freezing at -40C (using a Julabo chiller), the solution was converted into a thin film and subsequently the flask was connected to a freeze drier (conditions: vacuum 18 mTorr, condenser temperature -104.2 C) for 4 h to obtain a solid. DSC showed a broad endothermic peak at 184.7 C.XRPD confirmed the amorphous nature.

Reference： [1]Patent: WO2011/98258,2011,A1 .Location in patent: Page/Page column 31-32

52
[ 147-71-7 ]
[ 112984-60-8 ]
levoulifloxacin D-tartrate [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
	In dimethyl sulfoxide; at 20℃; for 20h;Resolution of racemate;	Example 1 Preparation of (S)-(-)-uliflourxacin; 105 g of racemic uliflourxacin was dissolved in 1,500 mL of dimethyl sulfoxide. 27 g of D-tartaric acid was dissolved in 405 mL of dimethyl sulfoxide dropwise while stirring. After stirring at room temperature for 20 hours, the precipitate was filtrated. The collected solid was dried under vacuum to obtain 86 g solid, which was recrystallized in dimethyl sulfoxide to obtain 37 g of levo<strong>[112984-60-8]ulifloxacin</strong>-D-tartrate, with C49.08%, H5.06%, N9.50%, S7.44% shown by elemental analysis (molecular formula: C16H16FN3O3S·1/2C4H6O6·H2O, calculated values: C48.86%, H4.78, N9.50%, S7.25%). Said salt was added into water to obtain a suspension, and the pH value was adjusted to 7-8 with 2% NaOH aqueous solution while stirring. After precipitation, filtration, and drying, 24.5 g of (S)-uliflourxacin was obtained, having a chemical name (S)-(-)-6-fluoro-1-methyl-4-oxo-(1-piperazinyl)-1H,4H-[1,3]thiazeto [3,2-alpha]quinoline-3-carboxylic acid. Specific rotation [alpha]20D= -133 (c=0.5, 0.1 mol/L methanesulfonic acid); 1H-NMR (DMSO-d6) delta2.11 (3H, d, j=6.2 Hz), 2.87 (4H, m), 3.19 (4H, m), 6.40 (1H, q, j=6.2 Hz), 6.89 (1H, d, j=7.4Hz), 7.79 (1H, d, j=13.9Hz), optical purity e.e. 96%.

Reference： [1]Patent: EP2524922,2012,A1 .Location in patent: Page/Page column 6

53
[ 147-71-7 ]
[ 84057-84-1 ]
2C₉H₇Cl₂N₅*C₄H₆O₆ [ No CAS ]

Reference： [1]CrystEngComm,2012,vol. 14,p. 7898 - 7906

54
[ 147-71-7 ]
[ 59803-98-4 ]
(5-bromoquinoxalin-6-yl)-(4,5-dihydro-1H-imidazol-2-yl)-amine L-tartrate [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
	In methanol; water;	The tartrate salt of brimonidine can be synthesized by adding (L)-(+)-tartaric acid to a solution of brimonidine in aqueous methanol. The brimonidine tartrate will separate out of solution.

Reference： [1]Patent: WO2011/53487,2011,A1 .Location in patent: Page/Page column 14

55
3-(R)-aminopiperidine dihydrochloride [ No CAS ]
[ 853029-57-9 ]
[ 147-71-7 ]
linagliptin-(D)-(-)-tartrate [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
79.5 g		1 -[(4-Methyl-quinazolin-2-yl)methyl]-3-methyl-7-(2-butyn-1 -yl)-8-bromoxanthine (100 gm) and methyl isobutyl ketone (MIBK, 1000 mL) were charged into a 2000 mL round bottomed flask equipped with a mechanical stirrer. Potassium carbonate (76.1 gm), (R)-piperidine-3-amine dihydrochloride (45.8 gm) and water (5 mL) were added to the reaction mixture at 26 C. The reaction mixture was heated to 95 C and maintained at that temperature for 6 hours. The reaction mixture was cooled to 30C and water (5 mL) was added to the reaction mixture and heated to 95 C and maintained for 5 hours. The reaction mixture was filtered and washed with MIBK (200 mL). The filtrate was charged into another flask and added 1000 mL of 6% aqueous acetic acid solution and stirred for 30 minutes at 28 C. The aqueous layer was separated and washed with 300 mL of toluene and 100 mL of 2-butanol. The aqueous layer was charged into another flask and 1000 mL of 2-butanol and 325 mL of 9% aqueous sodium hydroxide solution were added drop-wise at 28C (pH is 10.25). The mixture was stirred for one hour at 28 C and the organic layer was separated and the aqueous layer was extracted with 500 ml of 2-butanol. The combined 2-butanol layers were concentrated and 250 mL of 2-butanol was added to the residue and the resulted solution was concentrated. 400 mL of methanol was added to the residue and the resulted solution was heated to 48 C and stirred for 1 hour at 48C. The solution was cooled to 28C and 0.5 gm of linagliptin was seeded and the solution was cooled to 5C and maintained for 2 hours. The precipitation formed was filtered and washed with 100 mL of 2-butanol. The wet compound and 2500 mL were charged into 5000 mL round bottomed flask and the solution was heated to 40C and D-(-)-tartaric acid solution (19.9 gm of D-(-)-tartaric acid in 500 mL of methanol) was added slowly over a period of 30 minutes at 45C. the resulted solution was heated to reflux and stirred for 30 minutes. The solution was cooled to 12C and stirred for 3 hours. The precipitation formed was filtered and washed with 100 mL of methanol to get 172 gm of wet compound. The wet compound was dried under vacuum at 70 C for 7 hours to get 79.5 gm of Linagliptin-D-(-)-tartrate. XRPD pattern: Fig. 4, Chiral Purity: 99.96%, Regio impurity: 0.08%, Bromo impurity: 0.05%, (S)-isomer content: 0.04%, Tartaric acid content: 16.7%, Water content: 4.64%

Reference： [1]Patent: WO2013/98775,2013,A1 .Location in patent: Page/Page column 21; 22

56
[ 147-71-7 ]
[ 68-39-3 ]
[ 1449601-12-0 ]

Reference： [1]Heterocycles,2012,vol. 86,p. 1575 - 1582

57
[ 147-71-7 ]
[ 1443652-38-7 ]
[ 1443652-39-8 ]

Yield	Reaction Conditions	Operation in experiment
64%	With potassium phosphate; sodium chloride In tert-butyl methyl ether; water; isopropyl alcohol at 70℃; for 0.166667h;	3E Example 3E (4R)-2,2-dimethyl-7-(trifluoromethyl)chroman-4-amine, D-(-) tartaric acid salt A slurry of Example 3D (18.6 mmol) in MTBE (200 mL) was washed with 30% aqueous K3PO4 (200 mL) and brine (50 mL). The organic layer was dried (Na2SO4), filtered, concentrated, and diluted with IPA (33 mL). In a separate flask, D-(-)-tartaric acid (2.93 g, 19.5 mmol) and IPA (33 mL) were heated to 70° C. The amine solution was added slowly to the tartaric acid solution, keeping the temperature >70° C. After 10 minutes, the white slurry was cooled slowly to ambient temperature, filtered, washed with IPA (10 mL), and dried in a vacuum oven at 60° C. to give the title compound (4.72 g, 11.9 mmol, 64%). Chiral HPLC showed >99% ee. (DCI/NH3) m/z 229 (M-NH4)+.

Reference： [1]Current Patent Assignee: ABBVIE INC - US2013/158067, 2013, A1 Location in patent: Paragraph 0327

58
[ 147-71-7 ]
[ 1425093-39-5 ]
[ 1431285-47-0 ]

Yield	Reaction Conditions	Operation in experiment
93%	Stage #1: C₁₉H₃₁NOS With hydrogenchloride In ethyl acetate at 20℃; for 3h; Stage #2: D-tartaric acid In methanol for 1h; Reflux;	13.5 Step 5: Step 5: To a solution of compound 4 (1.6 g, 5.0 mmol) in ethyl acetate (10 mL) was added HCl-ethyl acetate (2 N, 10 mL), and the resulting solution was stirred at room temperature for 3 h. TLC analysis of the reaction mixture showed complete consumption of compound 3. The solvent was removed in vacuum. The residue was dissolved in water (10 mL), and pH was adjusted to 9-10 by a saturation aqueous solution of K2C03, extracted by ethyl acetate (3 x 20mL), dried, and concentrated to give a free amine. The free amine (1.1 g, 5.0 mmol) was dissolved in methanol (15 mL). D-tartaric acid (0.75 g, 5.0 mmol) was added to the solution,. The mixture was stirred under reflux for lh. The solution was slowly cooled to rt. The formed crystals were filtered to give product 5 (1.7 g, 93%).
93%	Stage #1: C₁₉H₃₁NOS With hydrogenchloride In ethyl acetate at 20℃; for 3h; Stage #2: With potassium carbonate In water Stage #3: D-tartaric acid In methanol for 1h; Reflux;	13.5 Step 5 To a solution of compound 4 (1.6 g, 5.0 mmol) in ethyl acetate (10 mL) was added HCl-ethyl acetate (2 N, 10 mL), and the resulting solution was stirred at room temperature for 3 h. TLC analysis of the reaction mixture showed complete consumption of compound 3. The solvent was removed in vacuum. The residue was dissolved in water (10 mL), and pH was adjusted to 9-10 by a saturation aqueous solution of K2CO3, extracted by ethyl acetate (3×20 mL), dried, and concentrated to give a free amine. The free amine (1.1 g, 5.0 mmol) was dissolved in methanol (15 mL). D-tartaric acid (0.75 g, 5.0 mmol) was added to the solution. The mixture was stirred under reflux for 1 h. The solution was slowly cooled to rt. The formed crystals were filtered to give product 5 (1.7 g, 93%). Mp. 172-174° C. The absolute stereochemistry of the compound 5 was determined by X-ray crystallography.

Reference： [1]Current Patent Assignee: COGNITION THERAPEUTICS INC - WO2013/29057, 2013, A2 Location in patent: Paragraph 0457
[2]Current Patent Assignee: COGNITION THERAPEUTICS INC - US2017/197977, 2017, A9 Location in patent: Paragraph 0629-0630

59
[ 147-71-7 ]
[ 1256388-51-8 ]
(1-{3-[6-(9,9-difluoro-7-{2-[5-(2-methoxycarbonylamino-3-methyl-butyryl)-5-aza-spiro[2.4]hept-6-yl]-3H-imidazol-4-yl}-9H-fluoren-2-yl)-1H-benzoimidazol-2-yl]2-aza-bicyclo[2.2.1]heptane-2-carbonyl}-2-methyl-propyl)carbamicacid methyl ester D-tartrate salt [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
65.6%	In ethyl acetate; at 23 - 50℃; for 16h;	6) As shown in equation , the reaction flask was added the formula (ix) Compound (10g, 11.2mmol) and ethyl acetate (70mL) mixed, stirred and dissolved at 50 deg.] C; the other D- tartaric acid (D-Tartaricacid) ( 1.5g, 10mmol) was dissolved in ethanol (70mL), and added dropwise to the above formula and (ix) a compound with a mixed solution of ethyl acetate, 50 precipitated crystals have a slow reaction, after cooling to 23 16h, the reaction was continued at least 3h after filtration, the cake washed with 40ml of a volume ratio of 1: 1 ethanol - ethyl acetate mixture was poured to wash the filter cake was pulled dry to give the formula (ix) of the target product, namely the Leidipawei D- tartrate, is 7.3g, the yield was 65.6%.
	at 0 - 20℃;	Example 4 Preparation of (1-{3-[6-(9,9-difluoro-7-{2-[5-(2-methoxycarbonylamino-3-methyl-butyryl)-5-aza-spiro[2.4]hept-6-yl]-3H-imidazol-4-yl}-9H-fluoren-2-yl)-1H-benzoimidazol-2-yl]-2-aza-bicyclo[2.2.1]heptane-2-carbonyl}-2-methyl-propyl)-carbamic acid D-tartrate (Compound I D-tartrate) [0183] Approximately 100-500 mg of Compound I Form I was transferred to each of a set of vials containing a magnetic stir bar. To each vial was added approximately 1.0-20 mL of acetonitrile (ACN) or isopropyl alcohol (IPA) until a clear solution was achieved. In a separate set of vials, clear ACN or IPA solutions of the acids listed in Table 4 below were prepared. [0184] Each of the acid solutions was added to a corresponding solution of Compound I in a dropwise fashion until 1 equivalent of acid had been. If resulting suspensions were observed, they were allowed to cool from ambient temperature to 0 C. If clear solutions were observed, they were allowed to slowly evaporate to assess possible crystallization. [0185] Among the acids screened, L-tartaric acid and HCl separately appeared to react with Compound I Form I and gave weak signs of crystallinity, as determined by PLM. However, the solid products from these two reactions proved to be unstable and lost crystallinity easily upon exposure to ambient atmosphere. [TABLE-US-00005] TABLE 4 Salt Screen for Compound I Acid pKa Observations HCl -6 Disordered salt formed Citric acid triacid, 3.1; 4.8; 6.4 No product formed Maleic acid diacid; 1.92; 6.23 Amorphous product L-tartaric acid diacid; 3.02; 4.36 Amorphous product formed D-tartaric acid diacid; 2.93; 4.23 Crystalline product formed fumaric acid diacid, 3.03; 4.38 No product formed Toluene sulfonic acidmonohydrate -1.34 No product formed Benzene sulfonic acid 0.7 No product formed Sulfuric acid -3 No product formed Succinic acid diacid, 4.2; 5.6 No product formed L-Malic acid diacid, 3.46; 5.1 No product formed D-Malic acid diacid, 3.46; 5.1 No product formed Malonic acid diacid, 2.83; 5.69 No product formed Oxalic acid diacid, 1.27; 4.28 amorphous product [0186] Even with a thorough crystalline form screen for L-tartrate, no stable crystalline product was successfully produced, as summarized below in Table 5. XRPD characterization of various samples resulting from the stable form screen for L-tartrate showed that the samples remained as amorphous solids in most solvents. In acetone, Compound I reverted back to the acetone solvate Form I as described above. [TABLE-US-00006] TABLE 5 Crystalline Form Screen Summary for Compound I L-tartrate Solvent 24 hr XRPD 2 week XRPD Observation Water Amorphous solid Amorphous solid Suspension IPAc Amorphous solid Amorphous solid Suspension MTBE Amorphous solid Amorphous solid Suspension 2-propanol Amorphous solid Amorphous solid Suspension THF N/A N/A Clear solution Acetone Compound I Compound I Suspension Form I Form I Methanol N/A N/A Clear solution ACN Amorphous solid Amorphous solid Suspension Ethanol N/A N/A Clear solution Ethyl acetate Amorphous solid Amorphous solid Suspension 2-MeTHF Amorphous solid Amorphous solid Suspension MEK Amorphous solid Amorphous solid Suspension MIBK Amorphous solid Amorphous solid Suspension n-heptane Amorphous solid Amorphous solid Suspension Toluene Amorphous solid Amorphous solid Suspension DCM Amorphous solid Amorphous solid Suspension aw of 0.8(EtOH/water) N/A N/A Clear solution [0187] Following these observations, D-tartaric acid was added to the acid list. Thus, when an IPA solution of D-tartaric acid was added to a solution of Compound I in IPA, a white suspension was generated immediately. A sample was filtered and characterized with XRPD, according to parameters described above, that clearly showed a crystalline product, (1-{3-[6-(9,9-difluoro-7-{2-[5-(2-methoxycarbonylamino-3-methyl-butyryl)-5-aza-spiro[2.4]hept-6-yl]-3H-imidazol-4-yl}-9H-fluoren-2-yl)-1H-benzoimidazol-2-yl]-2-aza-bicyclo[2.2.1]heptane-2-carbonyl}-2-methyl-propyl)-carbamic acid D-tartrate (Compound I D-tartrate). [0188] FIG. 9 shows the XRPD pattern of Compound I D-tartrate. The major peaks and corresponding relative intensities in the XRPD pattern diagram are listed below in Table 6 [TABLE-US-00007] TABLE 6 Major XRPD peaks for Compound I D-tartrate Position (2theta) Relative Intensity 4.0 87.8% 7.9 17.7% 9.1 38.9% 10.3 47.8% 12.7 30.6% 14.8 14.9% 15.8 13.2% 16.2 16.8% 16.9 15.4% 17.5 18.2% 18.3 26.4% 19.2 16.4% 19.7 100.0% 20.8 20.0% 21.0 27.2% 22.8 19.7% 24.0 30.9% 27.4 10.6% 28.2 5.6% [0189] The crystallinity of Compound I D-tartrate was further confirmed by a Polarized Light Microscopic (PLM) image of the crystals. [0190] The DSC curve of Compound I D-tartrate shows that upon heating this crystalline material has one sharp endotherm at 221.08 C., which indicates a clear melting event (FIG. 10). The TGA curve shows minimal weight loss, which indicates that Compound I D-tartrate is anhydrous. Dynamic vapor sorption (DVS) data demonstrated that Compound I D-tartrate tak...

Reference： [1]Patent: CN105237516,2016,A .Location in patent: Paragraph 0053; 0054; 0055; 0056
[2]Patent: US2013/324496,2013,A1 .Location in patent: Paragraph 0183-0190

60
[ 147-71-7 ]
[ 151213-40-0 ]
[ 151636-46-3 ]

Reference： [1]Spectrochimica Acta Part A: Molecular and Biomolecular Spectroscopy,2014,vol. 121,p. 254 - 258

61
[ 147-71-7 ]
[ 1323403-33-3 ]
C₂₅H₂₇N₃O₅*C₄H₆O₆ [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
	In acetonitrile; at 50 - 70℃; for 16.0h;	250 mg of Compound (I-S) was charged to 5 mL of acetonitrile. 83 mg (1 molar equivalent) of D-tartaric acid is charged. The reaction mixture was heated to 70 C., maintained at that temperature for 2 hours, then 50 C. for 14 hours, then cooled to 20 C. The D-tartrate was filtered and dried under vacuum.

Reference： [1]Patent: US2014/46057,2014,A1 .Location in patent: Paragraph 0641; 0642

62
[ 147-71-7 ]
[ 1323403-33-3 ]
(x)C₄H₆O₆*2C₂₅H₂₇N₃O₅ [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
	In acetonitrile; at 60 - 75℃; for 2.0h;	2 g of Compound (I-S) and 0.71 g of D-tartaric acid was added to 30 mL of acetonitrile. The mixture was heated for 60 C. for 1 hour and then 75 C. for 1 hour. The mixture was then cooled to 20 C., and the hemi D-tartrate wa collected.

Reference： [1]Patent: US2014/46057,2014,A1 .Location in patent: Paragraph 0643; 06444

63
[ 147-71-7 ]
[ 149-73-5 ]
[ 13171-64-7 ]

Reference： [1]Monatshefte fur Chemie,2014,vol. 145,p. 305 - 309

64
[ 274693-27-5 ]
[ 147-71-7 ]
(1S,2S,3R,5S)-3-[7-[(1R,2S)-2-(3,4-difluorophenyl)cyclopropyl]amino}-5-(propylthio)-3H-[1,2,3]-triazolo[4,5-d]pyrimidin-3-yl]-5-(2-hydroxyethoxyl)cyclopentane-1,2-diol D-tartrate [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
0.93%	In acetone at 0.3℃;	25 Preparation of Ticagrelor D-Tartrate Ticagrelor (0.5 g) and acetone (10 mL) were charged into a round bottom flask and the mixture was stirred at about 30° C. for about 15 minutes for clear solution. Then D (-)-tartaric acid (0.16 g) was added to the above reaction mixture at about 30° C. and mixture was stirred for overnight. To the clear solution, n-hexane (35 mL) was added and stirred for about 1 hour at 25-30° C. for solid separation. The solid was filtered, washed with n-hexane (5 mL) and dried to afford the title compound in about 93% yield having chiral HPLC purity of about 98%.

Reference： [1]Current Patent Assignee: DR REDDY'S LABORATORIES LIMITED - US2015/73146, 2015, A1 Location in patent: Paragraph 0213

65
[ 147-71-7 ]
5-bromo-8-methoxy-1-phenyl-3,4-dihydroisoquinoline [ No CAS ]
(1S)-5-bromo-8-methoxy-1-phenyl-1,2,3,4-tetrahydroisoquinoline tartrate [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
63%	Stage #1: 5-bromo-8-methoxy-1-phenyl-3,4-dihydroisoquinoline With borane-THF; (1R,2S)-1-Amino-2-indanol In tetrahydrofuran at 4 - 20℃; for 16h; Inert atmosphere; Stage #2: With trifluoroacetic acid In tetrahydrofuran for 2h; Inert atmosphere; Reflux; Stage #3: D-tartaric acid In isopropyl alcohol at 70 - 80℃; for 24h;	(1S)-5-Bromo-8-methoxy-1-phenyl-1,2,3,4-tetrahydroisoquinoline ((1S)-22) To a mixture of (1R,2S)-(+)-cis-1-Amino-2-indanol (1.9 g) in ether(60 mL) was added borane tetrahydrofuran complex (1.0 Min tetrahydrofuran solution 24 mL) at 4 °C under an argon atmosphere.3After the mixture was stirred at room temperature under an argon atmosphere for1 hour, compound 21 (3.1 g) was addedto the mixture at 4 °C. The mixture was stirred at room temperature for 16hours. Trifluoroacetic acid (15 mL) was added to the mixture and then heatedunder reflux for 2 hours. After cooling to room temperature, the mixture wasbasified with ammonia, extracted with chloroform, washed with brine, dried overmagnesium sulfate and then concentrated invacuo. The residue was dissolved in 2-propanol (60 mL). A solution ofD-(-)-tartaric acid (0.71 g) in 2-propanol (60 mL) was added to the mixture at70 °C and the resulting mixture was stirred overnight at 80 °C. After coolingto room temperature, the precipitate was filtered off to obtain compound (1S)-22 (2.42 g, 63%) as a colorless solid. HPLC (Chiralpak OD-RH [0.46 cm I.D.× 15 cm], MeCN: borate buffer (pH 9.0) = 45/55 flow rate 0.8 ml/min., columntemp.: 40 °C, UV: 230 nm): retention time: tr = 28.98 min (major), ts = 22.92min (minor); 97.7% ee. 1H NMR (DMSO-d6): δ 7.56(1H, d, J = 8.8 Hz), 7.20-7.33 (3H,m), 7.05-7.11 (2H, m), 6.85 (1H, d, J= 8.9 Hz), 5.34 (1H, s), 4.01 (1H, s), 3.55 (3H, s), 2.91-3.03 (1H, m), 2.71 (3H, brs); EI MS m/z: 317 [M]+.

Reference： [1]Ogiyama, Takashi; Yonezawa, Koichi; Inoue, Makoto; Katayama, Naoko; Watanabe, Toshihiro; Yoshimura, Seiji; Gotoh, Takayasu; Kiso, Tetsuo; Koakutsu, Akiko; Kakimoto, Shuichiro; Shishikura, Jun-Ichi [Bioorganic and Medicinal Chemistry, 2015, vol. 23, # 15, p. 4638 - 4648]

66
[ 3973-62-4 ]
[ 147-71-7 ]
(2S,3S)-3-carboxy-2,3-dihydroxypropionate (S)-3-phenylpiperidinium [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
0.35 g	In ethanol; water; at 70 - 75℃; for 0.166667h;	Synthesis of (S)-<strong>[3973-62-4]3-phenylpiperidine</strong> tartarate salt: 3-Carboxy-2,3-di ydroxy-propionate3-p enyl-piperidinium In a 100 mL two neck RB flask ethanol (20 mL), 3-Phenyl piperidine (0.3 g, 1.86 mmol), recovered from the above reaction, heating to 70-75 C. D-(-)-Tartaric acid (1.86 mmol) in 1 mL of water and 1 mL of ethanol added to reaction mixture, and stirred for 10 mins. Heating was stopped and allowed the reaction mixture to cool to 20-30 C. During this time, the material started to precipitated at around 45-50 C. Stirring was continued for additional 2 h at 20-30 C. The precipitate was filtered off, washed with ethanol. The solid was dried for 2 h under vacuum at 50 C, upon complete drying 0.35 g of pure material was obtained. Sp Rotation: -512' Chiral purity: 81% by chiral HPLC analysis on Chiracel OC column. Melting Point: 150-153 C

Reference： [1]Patent: WO2016/27284,2016,A2 .Location in patent: Page/Page column 75-76

67
L-1-phenyl-2-(1-pyrrolidinyl)-1-propanone-D-(-)-tartaric acid [ No CAS ]
[ 19134-50-0 ]
[ 147-71-7 ]

Yield	Reaction Conditions	Operation in experiment
82.31%	With hydrogenchloride; ammonia In water; ethyl acetate at 70℃; for 6h;	2.2 (2) racemization: the mother liquor vacuum distillation of isopropanol, add 100ml of water, add ammonia to pH 11,Add ethyl acetate extraction three times, water layer recovery D - (-) - tartaric acid, combined ethyl acetate layer plus 80ml water, addHydrochloric acid to a pH of 5, standing stratification, aqueous sodium hydroxide solution to pH 8.5, heated to 70 ° C,6 hours, plus sodium hydroxide solution to pH 11.5, ethyl acetate extraction three times, combined with acetic acidEthyl acetate layer, saturated brine, and evaporated to dryness to give DL-1-phenyl-2- (1-pyrrolidinyl) -1-propanoneAnd the yield was 82.31%.

Reference： [1]Current Patent Assignee: CHIFENG ARKER PHARMACEUTICAL TECH - CN105523984, 2016, A Location in patent: Paragraph 0037

68
[ 5891-21-4 ]
[ 773837-37-9 ]
[ 147-71-7 ]
[ 3886-69-9 ]
(2S,1'R)-N-(1'-phenylethyl)-α-methylprolinamide D-tartaric acid salt [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
24%	Stage #1: 5-chloro-2-pentanone; sodium cyanide; (R)-1-phenyl-ethyl-amine With acetic acid In water at 40℃; for 3h; Stage #2: With sulfuric acid In water; toluene at 60℃; for 6h; Stage #3: D-tartaric acid In methanol; ethyl acetate at 50℃;	9; 12 In a flask, 1.25 ml (11mmol) of 5-chloro-2-pentanone, The sodium cyanide 0.54g (11mmol), 1.28 ml (10mmol) of (R)-alpha methylbenzylamine, 0.63 ml (11mmol) of acetic acid, and 2.0 ml of water were prepared, and it was made to react at 40 degrees C for 3 hours. After adding 0.80 ml (10mmol) of NaOH aqueous solutions to reaction mixture 50 w/v%, it was made to react at 60 more degrees C for 2 hours. After cooling to a room temperature, the water layer was separated and light brown oil was obtained.[0170]The sulfuric acid 3.9g (40mmol) is taught to another flask, the above-mentioned light brown oil is added on a water bath, and it washed with 1.0 ml of toluene. After making it react at 60 degrees C for 6 hours, 2.0 ml of water and 6.4 ml of 50-w/v% NaOH aqueous solutions were slowly added on the water bath, and pH was set to ten. Ethyl acetate extracted, the organic layer was dried with magnesium sulfate, and the organic layer was condensed. Silica gel column chromatography refined concentration residue, and it obtained two fractionation, (2R,1'R)-N-(1'-phenylethyl)-alpha-methylprolinamide and (2S,1'R)-N-(1'-phenylethyl)-alpha-methylprolinamide. The stereochemistry of the 2nd place was derived and determined to optical activity alpha-methylproline (refer to reference example 2).[0171]1:0.48 g fractionation. They were (R [ 2 ], 1'R) :(2S, 1'R) =96:4, 85% of purity, 1.75mmol, and 18% of yield as a result of NMR analysis.2:1.52 g fractionation. They were (R [ 2 ], 1'R) :(2S, 1'R) =60:40, 88% of purity, 5.80mmol, and 58% of yield as a result of NMR analysis.

Reference： [1]Current Patent Assignee: MITSUBISHI CHEMICAL HOLDINGS CORPORATION - JP5959417, 2016, B2 Location in patent: Paragraph 0167-0171

69
[ 239463-72-0 ]
[ 147-71-7 ]
5-[(2R)-2-(tert-butoxycarbonyl)aminopropyl]-1-[3-(benzoyloxy)propyl]-2,3-dihydro-7-cyano-1H-indole [ No CAS ]
(R)-1-(1-(3-(benzoyloxy)propyl)-7-cyanoindolin-5-yl)propan-2-aminium (2S,3S)-3-carboxy-2,3-dihydroxypropanoate [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
97%	Stage #1: 5-[(2R)-2-(tert-butoxycarbonyl)aminopropyl]-1-[3-(benzoyloxy)propyl]-2,3-dihydro-7-cyano-1H-indole With hydrogenchloride In methanol at -5 - 20℃; Stage #2: 5-[(2R)-2-aminopropyl]-2,3-dihydro-1-[3-(benzoyloxy)propyl]-1H-indole-7-carbonitrile; D-tartaric acid In tetrahydrofuran	10; 11 In the - 5 - 0 °C lower, put in the reaction vessel to 1500 ml HCl/MeOH (10%), 463g compound 7, and then the room temperature reaction, liquid phase chromatographic monitoring to the reaction is complete (2 - 6 hours), the reaction liquid concentrate under reduced pressure to dry, the residue will be 1500 ml water dilution, for 5% of sodium hydroxide aqueous solution to adjust the pH of the diluent to the 8 - 9, the growth of dichloromethane extraction (1000 ml), collecting the organic layer is dried with anhydrous sodium sulfate, filtered, the filtrate is concentrated under reduced pressure to job 356g oil compound 8 , yield: 98%. In the reaction container input and the one on the oil of 356g compound 8, 147g L - tartaric acid, 1500 ml tetrahydrofuran, then heated to 50 - 60 °C the agitation dissolves clear, and then slowly cooled to room temperature, a large number of crystal, the obtained crystal filtering, vacuum dry to get 488g white crystal 1, yield: 97%.

Reference： [1]Current Patent Assignee: ZHEJIANG TIANYU PHARMACY CO., LTD. - CN106045895, 2016, A Location in patent: Paragraph 0029; 0124; 0125; 0126

70
[ 147-71-7 ]
[ 141109-14-0 ]
[ 141109-15-1 ]

Yield	Reaction Conditions	Operation in experiment
83.7%	In methanol; acetonitrile; butanone; for 11.5h;Reflux;	In 1L eggplant bottle in turn by adding dextral tartaric acid 270g (1.8mol), methanol 360ml, stirring and heating completely dissolved, the preparation of tartaric acid methanol solution.(1.8 mol) of the light brown oil (Compound III) prepared above, 1800 ml of acetonitrile and 192.75 g (1.62 mol) of methyl ethyl ketone were added to a 5 L three-necked flask, and the mixture was heated to reflux and the above tartaric acid Methanol solution, about 1.5h drop is completed, return to the state continue to stir more than 10h, down to room temperature, filtration, cake 40 drying 5h, weighing 550g, yield 83.7%,

Reference： [1]Patent: CN103467486,2016,B .Location in patent: Paragraph 0090; 0091

71
[ 147-71-7 ]
[ 28022-43-7 ]
(-)(+)-(4-chlorophenyl)phenyl-methane amine tartarate [ No CAS ]
(-)(-)-(4-chlorophenyl)phenyl-methane amine tartarate [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
1: 49% 2: 49%	In methanol at 60 - 65℃; for 0.0833333h;	2 Example 2 Preparation of diastereomeric salts of (4-chlorophenyl) -phenyl-methanamine 4.5 g (0.03 mol) of D - (-) - tartaric acid was dissolved in 63 mL of methanol at 60-65 ° C. 6.4 g (0.03 mol)Racemic (4-chlorophenyl) -phenyl-methylamine was added to a hot solution of D - (-) - tartaric acid in methanol. At this temperatureHeating was continued for 5 minutes. Then, the mixture of diastereoisomers was stirred for 3 hours without heating. The precipitated tartaric acid salt of (-) (-) (4-chlorophenyl) -phenyl-methylamine was filtered and washed with 10 mL of methanol on a filter, cooled to 10 ° C and dried and then recrystallized from methanol . The tartaric acid salt of the resulting (-) (-) (4-chlorophenyl) -phenyl-methylamine was 5.4 g (49%),The filtrate containing tartaric acid salt of (-) (+) - (4-chlorophenyl) -phenyl-methylamine was concentrated by distilling off methanol.The mixture was then cooled to room temperature and the precipitate of the tartaric acid salt of (-) (+) - (4-chlorophenyl) -phenyl-methylamine was filteredAnd washed with 5 mL of toluene on a filter and dried, followed by recrystallization from methanol. (-) (+) - (4-chlorophenyl) -Phenyl-methylamine tartrate 5.4 g (49%),
1: 49% 2: 49%	In methanol at 60 - 65℃; for 3.08333h;	2 Example 2 Production of diastereomeric salts of (4-chlorophenyl)-phenyl-methane amine 4.5 g (0.03 mol) of D-(-)-tartaric acid were dissolved in 63 mL ofmethanol at a temperature of 60-65°C. 6.4 g (0.03 mol) of racemic (4-chiorophenyl)-phenyl-methane amine were added to the hot methanol solution of D-(-)tartaric acid. Heating at that temperature continued for another 5 minutes. Then the mixture of diastereomers was stirred for 3 hours without heating. The precipitated tartrate of (-)(-)-(4-chiorophenyl)-phenyl-methane amine was filtered and rinsed on the filter with 10 mL of methanol cooled to 10° C. and dried, afier which it was recrystallized out of the methanol. The yield of tartrate of (-)(-)-(4-chlorophenyl)- phenyl-methane amine was 5.4 g (49%) expressed in terms ofa theoretical mass of racemic amine. Melting Point: Tm=179180° C.‘H Nuclear Magnetic Resonance Spectroscopy: ‘H NMR (300 MHz, D20), ö=5.6s (3H, NH3+), 7.3 (1H, CH), 7.4 (9H, Ag), 4.4 (2H, CH).‘3C Nuclear Magnetic Resonance Spectroscopy: ‘3C NMR (300 MHz, DMSO-d5), ö=130, 128.5,126.5, 125, 72, 57.10055] A filtrate containing a tartrate of (-)(+)-(4-chlo- rophenyl)-phenyl-methane amine was boiled down by boiling off the methanol, after which it was cooled to room temperature. The precipitate of the tartrate of(-)(+)-(4-chlo- rophenyl)-phenyl-methane amine was filtered, rinsed on the filter with 5 mL of toluene and dried, afier which it was recrystallized from the methanol. The yield of tartrate of (-)(+)-(4-chiorophenyl)-phenyl-methane amine was 5.4 g (49%) expressed in terms of a theoretical mass of racemic amine. Tm=163164° C. The NMR spectra of the tartrates of (-)(-)- and (-)(+)-(4-chiorophenyl)-phenyl-methane amine coincide.

Reference： [1]Current Patent Assignee: OOO SINTEGAL - CN105392775, 2016, A Location in patent: Paragraph 0053; 0054; 0055
[2]Current Patent Assignee: OOO SINTEGAL - US2016/244404, 2016, A1 Location in patent: Paragraph 0051; 0052; 0053; 0054; 0055; 0056; 0057

72
[ 147-71-7 ]
[ 1206161-97-8 ]
filgotinib D-tartrate [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
	In methanol; dichloromethane; at 50℃; for 1h;	Filgotinib free base (0.5 g) was dissolved in dichloromethane (13 ml) and methanol (2 ml), D-tartaric acid (0.19 g) was dissolved in dichloromethane (17 ml) and methanol (3 ml). The acid solution was dropped into the solution of filgotinib at 50C. The reaction mixture was stirred for 1 hour and then slowly cooled to 23C. The reaction mixture was stirred for 3 days, no salt formation could be observed.

Reference： [1]Patent: WO2017/12771,2017,A1 .Location in patent: Page/Page column 44

73
[ 147-71-7 ]
[ 379270-37-8 ]
9-[(R)-2-[[(S)-[[(S)-1-(isopropoxycarbonyl)ethyl]amino](phenoxy)phosphinyl]methoxy]propyl]adenine D-tartrate [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
	In acetonitrile; at 20℃;	10 mg (0.027 mmol) of (S)-isopropyl-2-(((S)-((((R)- 1 -(6-amino-911-purin-9-yl)propan-2- yl)oxy)methyl)Qthenoxy)phosphoryl)amino)propanoate was dissolved in 0.428 mL of acetonitrile. 4.2 mg (0.027 mmol) of tartaric acid was dissolved in 6.1 mL of acetonitrile. Both the solutions were mixed together and the obtained solution was left at the room temperature. During slow evaporation of the solvent a white crystalline substance wasseparated. The crystalline product was dried in a vacuum drier (200 mBar) at the room temperature for 2h. Melting point: 187°C (DSC). XRPD pattern: see Figure 22. JR spectrum:see Figure 24

Reference： [1]Patent: WO2016/192692,2016,A1 .Location in patent: Page/Page column 18

74
[ 147-71-7 ]
(1S,4R)-methyl 4-aminocyclopent-2-enecarboxylate L-hydrogen tartrate [ No CAS ]
[ 229177-52-0 ]

Yield	Reaction Conditions	Operation in experiment
88%	Stage #1: (1S,4R)-methyl 4-aminocyclopent-2-enecarboxylate L-hydrogen tartrate With sodium tetrahydroborate; water; sodium hydroxide at -5 - 0℃; for 4h; Stage #2: D-tartaric acid With sodium hydroxide In methanol at 65℃; for 0.5h;	4 Example 4: Preparation of ((1S,4R)-4-aminocyclopent-2-enyl)methanol-D-hydrogen tartrate To a solution of Aq. Sodium hydroxide was added sodium borohydride (0.8000 mol) and cooled to -5 to 0° C. (1S,4R)-methyl 4-aminocyclopent-2-enecarboxylate-L-hydrogen tartrate (0.343 mol) was added at -5 to 0° C. and maintained for 4 hrs at -5 to 0° C. Adjusted the pH to 12-13 with aq.sodium hydroxide solution. Extracted the reaction mass with n-butanol at room temperature. Butanol was completely distilled out below 50° C. under vacuum then added methanol and D-(-)-tartaric acid. Heated the mass to 65° C., maintained for 30 min and concentrated the mass to half volume. Allowed the mass to room temperature, and maintained for 3 hrs. Then filtered the mass and washed the cake with methanol. (Yield: 88%, HPLC purity: 99.91%).

Reference： [1]Current Patent Assignee: GRANULES INDIA LTD. - US2017/233329, 2017, A1 Location in patent: Paragraph 0046; 0047

75
[ 147-71-7 ]
[ 1187594-09-7 ]
{1-(ethylsulphonyl)-3-[4-(7H-pyrrolo[2,3-d]pyrimidin-4-yl)-1H-pyrazol-1-yl]azetidin-3-yl}acetonitrile tartarate [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
33.3%	In water; acetonitrile; at 20 - 22℃; for 2h;	0.5 g (1.35 mmol) { 1 -(ethylsulphonyl)-3 - [4-(7H-pyrrolo [2,3 -djpirimidin-4-yl)- 1H-pyrazol- 1- yljazetidin-3-yl}acetonitrile (baricitinib) is suspended in 22 ml of acetonitrile at 20-22 C,then while stirring a solution of 0.22 g (1.48 mmol; 1.1 mol equiv.) of D,L-tartaric acid made with 3 ml of water is added to it drop by drop. The reaction mixture is stirred for 2 hours at 20-22 C, then evaporated until dry. 25 ml of acetonitrile is added to the residue, and then stirred for 1 hour at 20-22 C. The precipitated solid material is filtered, washed on the filter with acetonitrile, then dried in the air at atmospheric pressure until constant weight isachieved. In this way 0.1 mg (33.3%) of a white coloured solid product is obtained. JR (KBr): 3142, 2258, 1694, 1631, 1599, 1350, 1328, 1137.?H-NMR (DMSO-d6, 400 MHz): 12.57 (b, 1H), 12.15 (bs, 1H), 8.93 (s, 1H), 8.71 (s, 1H), 8.48 (s, 1H), 7.63 (dd, 11=2.4 Hz, 12=3.5 Hz, 1H), 7.09 (dd, 11=1.6 Hz, 12=3.5 Hz,1H), 4.61 (d, 1=9.2 Hz, 2H), 4.31 (s, 2H), 4.24 (d, 1=9.2 Hz, 2H), 3.70 (s, 2H), 3.24(q, 1=7.4 Hz, 2H), 1.25 (t, 1=7.3 Hz, 3H).?3C-NMR (DMSO-d6, 100 MHz): 173.32, 152.38, 151.09, 149.55, 140.09, 129.80, 127.14, 122.41, 116.85, 113.24, 100.13, 72.33, 58.73, 56.25, 43.49, 27.02,7.62.Element analysis calculated for the formula C20H23N708S (M 521.51):C 46.06%; H 4.45%; N 18.80%; S 6.15%Measured: C 44.41%; H 4.56%; N 17.96%; S 6.21%.

Reference： [1]Patent: WO2017/125772,2017,A1 .Location in patent: Page/Page column 30

76
[ 147-71-7 ]
[ 42971-09-5 ]
C₂₂H₂₆N₂O₂*C₄H₆O₆ [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
	In methanol; at 0 - 40℃;	<strong>[42971-09-5]Vinpocetine</strong> (350 mg, 1 mmol) and D-tartaric acid (150 mg, 1 mmol) were added to a 50 ml Erlenmeyer flask at 0 C,Add 20ml of methanol, add in batches, when the solution has a slight turbidity, stop adding, stirring hours, directly heated to 40 C, a large number of solid precipitation, filtration drying, the product.

Reference： [1]Patent: CN106117198,2016,A .Location in patent: Paragraph 0012

77
[ 147-71-7 ]
[ 14252-80-3 ]
levobupivacaine D-tartrate [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
18.2 g	In ethanol; water; for 1h;Reflux;	25 g of bupivacaine (86.6 mmol),13 g (86.6 mmol) of D-tartaric acid were added to 300 mL of ethanol and 40 mL of waterMixed solvent, warmed to reflux, incubated 1h,Cooling crystallization, suction filtration, drying to obtain 18.2g levobupivacaine D-tartrate;The levobupivacaine D-tartrate was added to 300 mL of methanol,Dropwise adding 12mL ammonia (25wt%), stirring 2h, suction filtration,The filtrate was concentrated under reduced pressure to spin off levobupivacaine, which was dissolved in ethyl acetate,Hydrochloric acid ethanol solution was added dropwise to precipitate a solid, suction filtration,Drying left bupivacaine hydrochloride 14g, 90% yield. e.e. Value: 99.4%.

Reference： [1]Patent: CN106866501,2017,A .Location in patent: Paragraph 0054; 0056

78
[ 147-71-7 ]
[ 2867-59-6 ]
(R)-3-aminobutanol tartrate [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
30%	In methanol; at 20 - 60℃; for 6.0h;	The 3-aminobutanol (10) (200 g, 2.2471 mol) was dissolved with methanol (280 mL) at 25-27 C, and D-(-)-tartaric acid (252.96 g, 1.6853 mol) was added portion wise. The mixture was then heated at 55-60 C under stirring for 1h. Then the reaction mixture was slowly cooled to room temperature and stirring was continued for about 5 hrs. The reaction mixture was filtered and the formed cake was washed with methanol (100 mL) to give crude solid of (R)-3-aminobutanol tartrate (11) (187.97 g). The crude tartrate 11 was dissolved in about 2 L of methanol and slowly heated atabout 55-60 C until almost half of the solvent methanol evaporated to get a concentrated solution of 11. The product was filtered, washed with methanol to get compound 11 as awhite crystalline solid. Yield: 161.1g (30%). Purity was checked by GC: 99.2%. Chiral Purity by HPLC: 99.89%. Melting Point: 138-151 C; Retention time, [alpha]D26 = -15.68 (c=5.0 DM Water). 1H NMR (300 MHz, CDCl3) delta ppm: 3.95 (s, 2H), 3.48 (m, 2H), 3.29 (m, 1H), 1.75 (t, J = 6.3 Hz, 1H), 1.58 (m, J = 6.6 Hz, 1H), 1.98 (d, J = 6.6 Hz, 3H); IR(NEAT, cm-1): 3869, 3400, 2975, 2532, 1878, 1724, 1618, 1459, 1395, 1305, 1134, 1065, 1020; ESI-MS+: m/z 90.0938: ESI-MS-: m/z 149.0089.

Reference： [1]Letters in drug design and discovery,2017,vol. 14,p. 1371 - 1375

79
[ 147-71-7 ]
D-tartaric acid disodium salt [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
90%	With sodium hydroxide In methanol at 40℃; for 0.5h;	4.6 Synthesis of Na-tartrate For the synthesizing of the sodium tartrate salt, l-tartaric acid (0.1g, 0.66mmol) was stirred in 10ml MeOH at 40°C for 30min. The pH of the solution was adjusted to 7 by dropwise addition of NaOH solution (1M). The obtained white solid was filtered and thoroughly washed with MeOH (3×2ml) and dried at 60°C for 6h. The identity of Na-tart was established by FT-IR. Yield: 90% (138mg).

Reference： [1]Berijani, Kayhaneh; Farokhi, Afsaneh; Hosseini-Monfared, Hassan; Janiak, Christoph [Tetrahedron, 2018, vol. 74, # 18, p. 2202 - 2210]

80
[ 283173-50-2 ]
[ 147-71-7 ]
8-fluoro-2-{4-[(methylamino)methyl]phenyl}-1,3,4,5-tetrahydro-6H-azepino[5,4,3-cd]indol-6-one D-(-)-tartrate [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
1.07 g	In tetrahydrofuran; water; at 40 - 50℃;	lg of <strong>[283173-50-2]Rucaparib</strong> base (3.09 mmol), prepared according to the process described in Example 5, was dissolved in 15 mL of THF/H2O mixture (2: 1) while heating at 40-50°C. To the clear solution of <strong>[283173-50-2]Rucaparib</strong> base, 0.93 g (2 eq) of D-(-)- tartaric acid dissolved in 5 mL of water, was added while stirring at 40-50°C. Clear reaction mixture was then cooled down and crystallization occurred while stirring in ice bath. Obtained suspension was stirred for 1 hour at 0-5°C. Crystals were filtered off under vacuum and analyzed by XRPD as Form I of <strong>[283173-50-2]Rucaparib</strong> D-(-)-Tartrate. Wet crystals were dried in vacuum oven at 50°C for 4 hours to obtain 1.07 g of material, that was analyzed by XRPD as Form II of <strong>[283173-50-2]Rucaparib</strong> D-(-)-Tartrate. XRPD of <strong>[283173-50-2]Rucaparib</strong> D-(-)-Tartrate Form I is given in Figure 14. XRPD of <strong>[283173-50-2]Rucaparib</strong> D-(-)-Tartrate Form II is given in Figure 15.

Reference： [1]Patent: WO2018/140377,2018,A1 .Location in patent: Paragraph 00377-00380

81
[ 147-71-7 ]
[ 180916-16-9 ]
[ 190791-29-8 ]

Yield	Reaction Conditions	Operation in experiment
50%	In ethanol; for 0.08333330000000001h;Reflux;	Purified lasofoxifene (2 g) from step d was dissolved in 20 mL of 95ethanol, and mixed together with 0.78 g D-tartaric acid, which is dissolved in 7.8 mL of 95ethanol. The mixed solution was carefully heated to slight reflux for 5 minutes, and then cooled to room temperature. About 1.4 g precipitation of lasofoxifene D-tartrate salt was obtained (Yield 50) .[0163]Lasofoxifene D-tartrate was dissolved in DMSO-d6(50 mg/mL) for NMR analysis.1H NMR (600 MHz, DMSO-d6) delta 1.711.85 (m, 5H) , 2.08 (s, 1H) , 2.902.99 (m, 6H) , 3.17 (br, 2H) , 3.295 (m, 1H) , 4.024.06 (m, 4H) , 4.17 (d, J 3.6 Hz, lH) 4.43 (br, 2H) , 6.6 (m, 5H) , 6.81 (d, J 6.4 Hz, 2H) , 7.11 (s, 1H) , 7.13 (s, 2H) .13C NMR (150 MHz, DMSO-d6) delta 174.26, 155.74, 155.36, 144.12, 137.08, 135.37, 131.09, 130.97, 130.04, 127.83, 127.61, 125.87, 114.35, 113.58, 112.91, 71.90, 64.07, 53.59, 53.100, 49.40, 44.41, 29.244, 22.56, 22.41.

Reference： [1]Patent: WO2018/129645,2018,A1 .Location in patent: Paragraph 0140; 0146-0147

82
[ 147-71-7 ]
[ 22990-19-8 ]
[ 869884-00-4 ]
C₁₅H₁₅N*C₄H₆O₆ [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
	In ethanol; for 1h;Reflux;	In a 5 L reaction bottle, Adding 136.2 g of intermediate 3 and 136.1 g of racemic intermediate 3 a total of 272.3 g, D-tartaric acid 198.2 g, ethanol 2.35 L, and refluxing reaction for 1 h. The reaction solution was cooled to room temperature, filtered, and the cake was recrystallized from 930 ml of water. 185.0 g of a white solid intermediate 4 were obtained. Yield 39% (based on intermediate 3). The above two crystallized filtered filtrates were subjected to a free-spinning step.

Reference： [1]Patent: CN108329309,2018,A .Location in patent: Paragraph 0032; 0107

83
[ 31904-34-4 ]
[ 147-71-7 ]
C₁₄H₁₉FeN*C₄H₆O₆ [ No CAS ]
C₁₄H₁₉FeN*C₄H₆O₆ [ No CAS ]

Reference： [1]Chemistry - A European Journal,2018,vol. 24,p. 15223 - 15226

84
[ 147-71-7 ]
[ 1246765-22-9 ]
(R)-5-cyclopentylpyrazolidin-3-one D-tartrate [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
88%	In acetone at 20℃;	1.C Step C: R-5-cyclopentylpyrazolidin-3-one-D-tartrate To a solution of 5-cyclopentylpyrazolidin-3-one (278 g, 1.8 mol, 1.0 eq.) in acetone was added D-tartaric acid (135 g, 0.9 mol, 0.5 eq.) under stirring at room temperature, and stirred for 2 hours to precipitate crystals, and then filtrated. The filter cake was slurried with acetone five times, and forced air-dried at 50° C. to afford R-5-cyclopentylpyrazolidin-3-one-D-tartrate (241 g, yield: 88%, ee value: 99.5%).
40.7%	In acetone for 0.5h;	1.3 Step 3: Step 3: (R)-5-cyclopentylpyrazolidin-3-one D-tartrate 406 g of the racemic 5-cyclopentylpyrazolidin-3-one was added to 4.1 L of acetone, stirred and dissolved to obtain a clear solution, and then 198 g of D-tartaric acid was added thereto. After the resulting mixture was stirred for 30 minutes, the temperature was lowered to 0˜5° C. to crystallize. After filtration, the filter cake was rinsed with 1.5 L of acetone and then dried at 45° C. to obtain (R)-5-cyclopentylpyrazolidin-3-one D-tartrate (326 g, 40.7%) with an ee value of 99.4%.

Reference： [1]Current Patent Assignee: SHOUYAO HOLDINGS BEIJING CO LTD; SINO BIOPHARMACEUTICAL LIMITED - US2019/211021, 2019, A1 Location in patent: Paragraph 0103-0104
[2]Current Patent Assignee: SINO BIOPHARMACEUTICAL LIMITED - US2019/23712, 2019, A1 Location in patent: Paragraph 0236

85
[ 147-71-7 ]
[ 1341200-45-0 ]
C₂₄H₃₀ClN₇O₂S*2C₄H₆O₆ [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
	With methoxybenzene; In ethanol; at 70℃;	The reprocessing procedure included dissolving 1C in a chloroform and ethanol mixture and activated charcoal was added. The resulting slurry was stirred at room temperature for 1 hour and filtered. The filtered solid was washed, combined with filtrate and the solvents were removed by distillation. Then ethanol was added, and distillation repeated to remove chloroform. After the distillation, resulting slurry was cooled and filtered to give purified 1C. The obtained material was dissolved with mixture of anisole and ethanol at 70C. Ethanol solution of tartaric acid was then added to this solution and subsequently seeded with Form A. The resulting slurry is cooled to 20C and filtered, washed with ethanol, dried to afford the polymorph of a tartaric acid salt of a compound of structure (I). The purity of the desired product was assessed to be 99.5% by HPLC. 1H NMR (400 MHz, DMSO-d 1H), 8.29 (s, 1H), 7.83 (dd, J = 8.0, 1.6 Hz, 1H), 7.71 (td, J = 7.2, 1.4 Hz), 7.57 (d, J = 8.4 Hz, 2H), 7.38 (td, J = 7.2 Hz, J = 1.0 Hz), 7.18 (d, J = 8.4 Hz, 2H), 4.19 (s, 4H), 3.51 (s, 2H), 2.86 (bs, 3H),2.65 (s, 6H), 2.60-2.50 (m, 8H)

Reference： [1]Patent: WO2019/195753,2019,A1 .Location in patent: Page/Page column 193-194

86
[ 79-37-8 ]
[ 147-71-7 ]
C₁₀H₁₀O₁₄ [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
92.3%	With triethylamine In toluene at 55℃; for 5h;	1-4 Example 1: Combine D-tartaric acid (19.5 g, 0.13 mol), 70 mL toluene, triethylamine (12.1 g, 0.12 mol),Add to a 250 mL four-necked flask equipped with a thermometer, mechanical stirring and condensation device,Heat and stir, add oxalyl chloride (6.3g, 0.05 mol) dropwise at 55 , keep the reaction for 5 h,After cooling to room temperature, the solid was collected by filtration to obtain the crude product, which was recrystallized from ethyl acetate.16.3 g of solid was obtained with a yield of 92.3%.

Reference： [1]Current Patent Assignee: JINAN UNIVERSITY (GUANGZHOU) - CN110878021, 2020, A Location in patent: Paragraph 0014-0017

87
(2S,3S)-diethyl 2,3-diacetoxysuccinate [ No CAS ]
[ 147-71-7 ]

Yield	Reaction Conditions	Operation in experiment
91.2%	With water; sodium hydroxide In N,N-dimethyl-formamide at 60℃; for 10h;	1.C; 6-8 C. Preparation of D-(-)-tartaric acid () Add (2S, 3S) -2,3-diacetoxy diethyl succinate (II) (290g, 1.0mol) and 5% strength sodium hydroxide aqueous solution (2900g) to the reactor After heating to 60 , and then continue to stir the reaction for 10 hours,After the reaction is completed, it is cooled to room temperature,Under stirring, slowly add 5% concentration of dilute hydrochloric acid to adjust the pH of the mixed solution to 2-3,Then filter to remove insoluble materials, and then remove most of the solvent by vacuum distillationAdd a small amount of D-(-)-tartaric acid () seed crystals, stir and crystallize and then let stand overnight,The precipitated crystals are collected by filtration and after dryingD-(-)-tartaric acid (I) was obtained at 136.8 g, and the yield was about 91.2%.99.56% purity (titrated with 0.5mol / L sodium hydroxide solution),Specific optical rotation [α] D25 ° C: -12.3 °.
91.2%	With water; sodium hydroxide In N,N-dimethyl-formamide at 60℃; for 10h;	1.C; 6-8 C. Preparation of D-(-)-tartaric acid () Add (2S, 3S) -2,3-diacetoxy diethyl succinate (II) (290g, 1.0mol) and 5% strength sodium hydroxide aqueous solution (2900g) to the reactor After heating to 60 , and then continue to stir the reaction for 10 hours,After the reaction is completed, it is cooled to room temperature,Under stirring, slowly add 5% concentration of dilute hydrochloric acid to adjust the pH of the mixed solution to 2-3,Then filter to remove insoluble materials, and then remove most of the solvent by vacuum distillationAdd a small amount of D-(-)-tartaric acid () seed crystals, stir and crystallize and then let stand overnight,The precipitated crystals are collected by filtration and after dryingD-(-)-tartaric acid (I) was obtained at 136.8 g, and the yield was about 91.2%.99.56% purity (titrated with 0.5mol / L sodium hydroxide solution),Specific optical rotation [α] D25 ° C: -12.3 °.

Reference： [1]Current Patent Assignee: CHANGZHOU CHUANYOU ENVIRONMENTAL PROTECTION TECH - CN111057000, 2020, A Location in patent: Paragraph 0016; 0038-0046
[2]Current Patent Assignee: ZHEJIANG GENEBEST PHARMACEUTICAL - CN108084064, 2020, B Location in patent: Paragraph 0016; 0038-0046

88
[ 147-71-7 ]
[ 78687-39-5 ]
nicotinamide-β-D-ribofuranoside D-hydrogen tartrate [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
70%	Stage #1: D-tartaric acid With triethylamine In methanol at 0 - 20℃; Sealed tube; Stage #2: 3-carbamoyl-1-((2R,3R,4S,5R)-3,4-dihydroxy-5-(hydroxymethyl)tetrahydrofuran-2-yl)pyridin-1-ium bromide In methanol Heating; Sealed tube;	Example 12a: Use of triethylammonium·L-hydrogen malate General procedure: 3.50 g (26.1 mmol) of L-malic acid were dissolved in 10 mL methanol with stirring. The solution was cooled in an ice bath and 3.64 mL of triethylamine (26.1 mmol, 1 eq) added. The pH of the slightly yellowish solution was around 4.5. 15 mL of a 1.73 molar solution of Et3N·L-hydrogen malate were prepared. 5.80 g (17.3 mmol) of nicotinamide-β-D-ribofuranoside bromide were suspended in 10 mL of methanol upon stirring. 10 mL (17.3 mmol, 1 eq) of the 1.73 molar solution of triethylammonium L-hydrogen malate were added. The suspension was heated until the solids dissolved completely. After cooling, a white solid precipitated. The suspension was stirred for 30 min and then filtered. The residue was washed with methanol and dried in vacuo at 35 °C. Nicotinamide-beta-D-ribofuranoside·L-hydrogen malate was isolated as a white crystalline powder (4.15 g, 62%). Mp: 116.5-117 °C. IC: Residual bromide 0.10%.

Reference： [1]Haase, Robert; Hery-Barranco, Adrian; Pala, Laura; Parris, Jaclyn; Schabert, Günter; Spingler, Bernhard; Spitz, Urs [Molecules, 2021, vol. 26, # 9]

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P353	Rinse skin with water/shower.
P360	Rinse immediately contaminated clothing and skin with plenty of water before removing clothes.
P361	Remove/Take off immediately all contaminated clothing.
P362	Take off contaminated clothing and wash before reuse.
P363	Wash contaminated clothing before reuse.
P370	In case of fire:
P371	In case of major fire and large quantities:
P372	Explosion risk in case of fire.
P373	DO NOT fight fire when fire reaches explosives.
P374	Fight fire with normal precautions from a reasonable distance.
P376	Stop leak if safe to do so. Oxidising gases (section 2.4) 1
P377	Leaking gas fire: Do not extinguish, unless leak can be stopped safely.
P378
P380	Evacuate area.
P381	Eliminate all ignition sources if safe to do so.
P390	Absorb spillage to prevent material damage.
P391	Collect spillage. Hazardous to the aquatic environment
P301 + P310	IF SWALLOWED: Immediately call a POISON CENTER or doctor/physician.
P301 + P312	IF SWALLOWED: call a POISON CENTER or doctor/physician IF you feel unwell.
P301 + P330 + P331	IF SWALLOWED: Rinse mouth. Do NOT induce vomiting.
P302 + P334	IF ON SKIN: Immerse in cool water/wrap in wet bandages.
P302 + P350	IF ON SKIN: Gently wash with plenty of soap and water.
P303 + P361 + P353	IF ON SKIN (or hair): Remove/Take off Immediately all contaminated clothing. Rinse SKIN with water/shower.
P304 + P312	IF INHALED: Call a POISON CENTER or doctor/physician if you feel unwell.
P304 + P340	IF INHALED: Remove victim to fresh air and Keep at rest in a position comfortable for breathing.
P304 + P341	IF INHALED: If breathing is difficult, remove victim to fresh air and keep at rest in a position comfortable for breathing.
P305 + P351 + P338	IF IN EYES: Rinse cautiously with water for several minutes. Remove contact lenses, if present and easy to do. Continue rinsing.
P306 + P360	IF ON CLOTHING: Rinse Immediately contaminated CLOTHING and SKIN with plenty of water before removing clothes.
P307 + P311	IF exposed: call a POISON CENTER or doctor/physician.
P308 + P313	IF exposed or concerned: Get medical advice/attention.
P309 + P311	IF exposed or if you feel unwell: call a POISON CENTER or doctor/physician.
P332 + P313	IF SKIN irritation occurs: Get medical advice/attention.
P333 + P313	IF SKIN irritation or rash occurs: Get medical advice/attention.
P335 + P334	Brush off loose particles from skin. Immerse in cool water/wrap in wet bandages.
P337 + P313	IF eye irritation persists: Get medical advice/attention.
P342 + P311	IF experiencing respiratory symptoms: call a POISON CENTER or doctor/physician.
P370 + P376	In case of fire: Stop leak if safe to Do so.
P370 + P378	In case of fire:
P370 + P380	In case of fire: Evacuate area.
P370 + P380 + P375	In case of fire: Evacuate area. Fight fire remotely due to the risk of explosion.
P371 + P380 + P375	In case of major fire and large quantities: Evacuate area. Fight fire remotely due to the risk of explosion.
Storage
Code	Phrase
P401
P402	Store in a dry place.
P403	Store in a well-ventilated place.
P404	Store in a closed container.
P405	Store locked up.
P406	Store in corrosive resistant/ container with a resistant inner liner.
P407	Maintain air gap between stacks/pallets.
P410	Protect from sunlight.
P411
P412	Do not expose to temperatures exceeding 50 oC/ 122 oF.
P413
P420	Store away from other materials.
P422
P402 + P404	Store in a dry place. Store in a closed container.
P403 + P233	Store in a well-ventilated place. Keep container tightly closed.
P403 + P235	Store in a well-ventilated place. Keep cool.
P410 + P403	Protect from sunlight. Store in a well-ventilated place.
P410 + P412	Protect from sunlight. Do not expose to temperatures exceeding 50 oC/122oF.
P411 + P235	Keep cool.
Disposal
Code	Phrase
P501	Dispose of contents/container to ...
P502	Refer to manufacturer/supplier for information on recovery/recycling

Physical hazards
Code	Phrase
H200	Unstable explosive
H201	Explosive; mass explosion hazard
H202	Explosive; severe projection hazard
H203	Explosive; fire, blast or projection hazard
H204	Fire or projection hazard
H205	May mass explode in fire
H220	Extremely flammable gas
H221	Flammable gas
H222	Extremely flammable aerosol
H223	Flammable aerosol
H224	Extremely flammable liquid and vapour
H225	Highly flammable liquid and vapour
H226	Flammable liquid and vapour
H227	Combustible liquid
H228	Flammable solid
H229	Pressurized container: may burst if heated
H230	May react explosively even in the absence of air
H231	May react explosively even in the absence of air at elevated pressure and/or temperature
H240	Heating may cause an explosion
H241	Heating may cause a fire or explosion
H242	Heating may cause a fire
H250	Catches fire spontaneously if exposed to air
H251	Self-heating; may catch fire
H252	Self-heating in large quantities; may catch fire
H260	In contact with water releases flammable gases which may ignite spontaneously
H261	In contact with water releases flammable gas
H270	May cause or intensify fire; oxidizer
H271	May cause fire or explosion; strong oxidizer
H272	May intensify fire; oxidizer
H280	Contains gas under pressure; may explode if heated
H281	Contains refrigerated gas; may cause cryogenic burns or injury
H290	May be corrosive to metals
Health hazards
Code	Phrase
H300	Fatal if swallowed
H301	Toxic if swallowed
H302	Harmful if swallowed
H303	May be harmful if swallowed
H304	May be fatal if swallowed and enters airways
H305	May be harmful if swallowed and enters airways
H310	Fatal in contact with skin
H311	Toxic in contact with skin
H312	Harmful in contact with skin
H313	May be harmful in contact with skin
H314	Causes severe skin burns and eye damage
H315	Causes skin irritation
H316	Causes mild skin irritation
H317	May cause an allergic skin reaction
H318	Causes serious eye damage
H319	Causes serious eye irritation
H320	Causes eye irritation
H330	Fatal if inhaled
H331	Toxic if inhaled
H332	Harmful if inhaled
H333	May be harmful if inhaled
H334	May cause allergy or asthma symptoms or breathing difficulties if inhaled
H335	May cause respiratory irritation
H336	May cause drowsiness or dizziness
H340	May cause genetic defects
H341	Suspected of causing genetic defects
H350	May cause cancer
H351	Suspected of causing cancer
H360	May damage fertility or the unborn child
H361	Suspected of damaging fertility or the unborn child
H361d	Suspected of damaging the unborn child
H362	May cause harm to breast-fed children
H370	Causes damage to organs
H371	May cause damage to organs
H372	Causes damage to organs through prolonged or repeated exposure
H373	May cause damage to organs through prolonged or repeated exposure
Environmental hazards
Code	Phrase
H400	Very toxic to aquatic life
H401	Toxic to aquatic life
H402	Harmful to aquatic life
H410	Very toxic to aquatic life with long-lasting effects
H411	Toxic to aquatic life with long-lasting effects
H412	Harmful to aquatic life with long-lasting effects
H413	May cause long-lasting harmful effects to aquatic life
H420	Harms public health and the environment by destroying ozone in the upper atmosphere

[ CAS No. 147-71-7 ] {[proInfo.proName]}

Quality Control of [ 147-71-7 ]

Related Doc. of [ 147-71-7 ]

Product Details of [ 147-71-7 ]

Calculated chemistry of [ 147-71-7 ]

Physicochemical Properties

Pharmacokinetics

Lipophilicity

Druglikeness

Water Solubility

Medicinal Chemistry

Safety of [ 147-71-7 ]

Application In Synthesis of [ 147-71-7 ]

[ 147-71-7 ] Synthesis Path-Upstream 1~9

[ 147-71-7 ] Synthesis Path-Downstream 1~88

Related Functional Groups of [ 147-71-7 ]

Aliphatic Chain Hydrocarbons

Alcohols

Carboxylic Acids

Precautionary Statements-General

Prevention

Response

Storage

Disposal

Physical hazards

Health hazards

Environmental hazards

Inquiry

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[ 147-71-7 ]