[ CAS No. 101930-07-8 ] {[proInfo.proName]}

Name: 101930-07-8|(R)-3-Hydroxy-1-benzylpyrrolidine|95%
Brand: Ambeed
SKU: A818005
Price: 12.0 USD
Availability: InStock
Rating: 97 (29 reviews)

,{[proInfo.pro_purity]}

Cat. No.: {[proInfo.prAm]}

DV 2D 3D

3d Animation Molecule Structure of 101930-07-8

Structure of 101930-07-8 * Storage: {[proInfo.prStorage]}

Cart0 Add to My Favorites Add to My Favorites Bulk Inquiry Inquiry Add To Cart

Search after Editing

* Storage: {[proInfo.prStorage]}

For Research Only 110K+ Compounds Competitive Price 1-2 Day Shipping

Quality Control of [ 101930-07-8 ]

COA NMR CNMR HPLC LC-MS

Related Doc. of [ 101930-07-8 ]

SDS Specification

Alternatived Products of [ 101930-07-8 ]

Product Details of [ 101930-07-8 ]

CAS No. :	101930-07-8	MDL No. :	MFCD00075484
Formula :	C₁₁H₁₅NO	Boiling Point :	-
Linear Structure Formula :	-	InChI Key :	YQMXOIAIYXXXEE-LLVKDONJSA-N
M.W :	177.24	Pubchem ID :	643472
Synonyms :

Calculated chemistry of [ 101930-07-8 ]

Physicochemical Properties

Num. heavy atoms :	13
Num. arom. heavy atoms :	6
Fraction Csp3 :	0.45
Num. rotatable bonds :	2
Num. H-bond acceptors :	2.0
Num. H-bond donors :	1.0
Molar Refractivity :	56.49
TPSA :	23.47 Å²

Pharmacokinetics

GI absorption :	High
BBB permeant :	Yes
P-gp substrate :	No
CYP1A2 inhibitor :	No
CYP2C19 inhibitor :	No
CYP2C9 inhibitor :	No
CYP2D6 inhibitor :	No
CYP3A4 inhibitor :	No
Log Kp (skin permeation) :	-6.48 cm/s

Lipophilicity

Log Po/w (iLOGP) :	2.17
Log Po/w (XLOGP3) :	1.27
Log Po/w (WLOGP) :	0.72
Log Po/w (MLOGP) :	1.46
Log Po/w (SILICOS-IT) :	1.76
Consensus Log Po/w :	1.48

Druglikeness

Lipinski :	0.0
Ghose :	None
Veber :	0.0
Egan :	0.0
Muegge :	1.0
Bioavailability Score :	0.55

Water Solubility

Log S (ESOL) :	-1.95
Solubility :	2.0 mg/ml ; 0.0113 mol/l
Class :	Very soluble
Log S (Ali) :	-1.36
Solubility :	7.7 mg/ml ; 0.0435 mol/l
Class :	Very soluble
Log S (SILICOS-IT) :	-2.44
Solubility :	0.645 mg/ml ; 0.00364 mol/l
Class :	Soluble

Medicinal Chemistry

PAINS :	0.0 alert
Brenk :	0.0 alert
Leadlikeness :	1.0
Synthetic accessibility :	1.57

Safety of [ 101930-07-8 ]

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 [ 101930-07-8 ]

* 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.

Downstream synthetic route of [ 101930-07-8 ]

[ 101930-07-8 ] Synthesis Path-Downstream 1~43

1
[ 124-63-0 ]
[ 101930-07-8 ]
[ CAS Unavailable ]

Yield	Reaction Conditions	Operation in experiment
100%	With triethylamine In dichloromethane at 0℃; for 3h;
97%	With triethylamine In ethyl acetate for 3h; cooling;
96.7%	With triethylamine In tetrahydrofuran at -10 - 0℃; for 4h;

96.4%	Stage #1: (R)-N-benzyl-3-hydroxypyrrolidine With triethylamine In dichloromethane at 0℃; Stage #2: methanesulfonyl chloride In dichloromethane at 20℃; for 2h;	31 PREPARATIVE EXAMPLE 31 [1508] 1N-Benzyl-3(R)-hydroxy-pyrrolidines (5 g, 28.21 mmol) and triethylamine (7.86 mL, 56.35 mmol) were dissolved in CH2Cl2 (50 mL) and the mixture was stirred under nitrogen at 0° C. Methanesulfonylchloride (2.62 mL, 33.87 mmol) was added and the solution was stirred at room temperature for 2 h. The solution was diluted with CH2Cl2 and washed with saturated aqueous sodium bicarbonate, water and dried (MgSO4), filtered and evaporated to dryness to give the (R) title compound (7.2 g, 96.4%). FABMS (M+1)=256; 1HNMR (CDCl3) 2.2 (m, 1H), 2.3 (m, 1H), 2.52 (m, 1H), 2.7-2.85 (m, 3H), 2.95 (s, 3H), 3.65 (q, 2H), 5.16 (m, 1H), 7.3 (s, 5H).
95%	With triethylamine In dichloromethane at 0 - 20℃; for 2.5h;	1.3 Step 3: Preparation of (3R)-1-benzyl-3-[(methylsulfonyl)oxy]pyrrolidine The compound (3R)-L-BENZYL-PYRROLIDIN-3-OL (1.0 g, 5.65 mM) was dissolved in triethylamine (2.0 ml, 14.3 mM), and dimethyl amino pyridine (DMAP) (0.002 g), dichloromethane (20.0 ml) and methanesulfonyl chloride (0.9 ml, 11.7 MM) was added dropwise at 0-5°C. The reaction mixture was maintained at the same temperature for about half an hour. The reaction mixture was then stirred at room temperature for 2 hours. The reaction mixture was diluted with dichloromethane (50.0 ml), washed with saturated sodium bicarbonate and brine solution. It was further dried over anhydrous sodium sulphate and concentrated to get the title compound as oil. Yield = 95% (1.2 g, 5.38 mM). This material was used as such in the next step.
84%	With triethylamine In dichloromethane 1.) 0 deg C, 20 min, 2.) room temperature, 1.5 h;
68%	With triethylamine In toluene at 5 - 20℃; for 2.16667h;
	With Et₃ In toluene
	With triethylamine
	With triethylamine In water; toluene	6 (R)-1-Benzyl-3-mesyloxypyrrolidine (R)-1-Benzyl-3-mesyloxypyrrolidine (R)-1-Benzyl-3-hydroxypyrrolidine (3.9 g, 22 mmol) was dissolved in toluene (100 mL) and the solution stirred and cooled to 0°-5° C. Triethylamine (2.66 g, 26.2 mmol) was added followed by methanesulfonyl chloride (3.0 g, 26 mmol). A slurry formed after 30 minutes. The mixture was allowed to warm to room temperature and stirred overnight. Water (100 mL) was added to the reaction mixture and the organic layer separated and washed with water (100 mL) and concentrated under reduced pressure to give (R)-1-benzyl-3-mesyloxypyrrolidine (5.7 g) as a yellow oil: 1 H-NMR (CDCl3), 60 MHz): δ1.9-2.7 (m, 4H), 2.78 (d, 2H, J=15), 2.90 (s, 3H), 3.65 (s, 2H), 4.9-5.3 (m, 1H), 7.28 (s, 5H).
	In triethylamine; toluene	7.a Example 7 a) 10 g of (R)-1-(phenylmethyl)-3-pyrrolidinol were dissolved in 160 ml of anhydrous toluene. The solution was stirred under a stream of nitrogen, cooled in an ice/ethanol bath and 8.7 ml of triethylamine were added. At a temperature of -5 0C 4,9 ml of a solution of methanesulfonylchloride in 110 ml of anhydrous toluene were added dropwise over 1,5 hours and the reaction mixture was stirred for 1 hour at 0 0C. The solid was filtered and washed with ethyl acetate. The filtrate was washed with water, dried and evaporated in vacuo to give 13,9 g of (R)-3-methanesulfonyloxy-1-(phenylmethyl)-pyrrolidine as an almost colourless oil. M.S. (C.I.) (M/Z): 256 [M+H]+.
	In triethylamine; toluene	7.a Example 7 a) 10 g of (R)-1-(phenylmethyl)-3-pyrrolidinol were dissolved in 160 ml of anhydrous toluene. The solution was stirred under a stream of nitrogen, cooled in an ice/ethanol bath and 8.7 ml of triethylamine were added. At a temperature of -5° C. 4,9 ml of a solution of methanesulfonylchloride in 110 ml of anhydrous toluene were added dropwise over 1,5 hours and the reaction mixture was stirred for 1 hour at 0° C. The solid was filtered and washed with ethyl acetate. The filtrate was washed with water, dried and evaporated in vacuo to give 13,9 g of (R)-3-methanesulfonyloxy-1-(phenylmethyl)-pyrrolidine as an almost colourless oil. M.S. (C.I.) (M/Z): 256 [M+H]+. In a similar way were prepared:

Reference： [1]Adams; Duncton [Synthetic Communications, 2001, vol. 31, # 13, p. 2029 - 2036]
[2]Muraglia, Marilena; Franchini, Carlo; Corbo, Filomena; Scilimati, Antonio; Sinicropi, Maria Stefania; De Luca, Annamaria; De Bellis, Michela; Camerino, Diana Conte; Tortorella, Vincenzo [Journal of Heterocyclic Chemistry, 2007, vol. 44, # 5, p. 1099 - 1103]
[3]Huang; Luedtke; Freeman; Wu; Mach [Journal of Medicinal Chemistry, 2001, vol. 44, # 11, p. 1815 - 1826]
[4]Current Patent Assignee: LIGAND PHARMACEUTICALS INC - US2003/229099, 2003, A1 Location in patent: Page 176
[5]Current Patent Assignee: SUN PHARMACEUTICAL INDUSTRIES LIMITED - WO2004/56767, 2004, A1 Location in patent: Page 14-15
[6]Rosen, Terry; Chu, Daniel T. W.; Lico, Isabella M.; Fernandes, Prabhavathi B.; Shen, Linus; et al. [Journal of Medicinal Chemistry, 1988, vol. 31, # 8, p. 1586 - 1590]
[7]Current Patent Assignee: DAIICHI SANKYO COMPANY, LIMITED - US6337405, 2002, B1 Location in patent: Example 1
[8]Fedij, Victor; Lenoir, Edward A.; Suto, Mark J.; Zeller, James R.; Wemple, James [Tetrahedron Asymmetry, 1994, vol. 5, # 7, p. 1131 - 1134]
[9]Gmeiner, Peter; Orecher, Florian; Thomas, Christoph; Weber, Klaus [Tetrahedron Letters, 1995, vol. 36, # 3, p. 381 - 382]
[10]Current Patent Assignee: PFIZER INC - US5347017, 1994, A
[11]Current Patent Assignee: MERCK & CO INC - EP863136, 1998, A1
[12]Current Patent Assignee: MERCK & CO INC - US6281243, 2001, B1

2
[ 116143-02-3 ]
[ 101930-07-8 ]

Yield	Reaction Conditions	Operation in experiment
100%	With water; sodium hydroxide at 20℃; for 1h;	Inversion at C-3 of (3S)-N-benzyl-3-hydroxypyrrolidine (S)-1 To a solution of 0.50 g (1.51 mmol) of (S)-6 in 2 ml of dry dimethyl sulfoxide, 0.25 g (3.05 mmol) of anhydrous sodium acetate was added. The mixture was stirred at 120 C for 2 h. The reaction was monitored by HPLC. After cooling to room temperature, the mixture was diluted with water. The aqueous layer was extracted with dichloromethane (3 0.5 mL). The organic layers were combined, dried over sodium sulfate and concentrated at reduced pressure to give 0.31 g (1.42 mmol) of (R)-3, (94% yield, 95% ee). To this residue, 1 ml (80 mmol) of 2 M sodium hydroxide solution was added. This mixture was stirred at room temperaturefor 1 h and then the aqueous layer was extracted with dichloromethane (3 x 0.5 mL). The organic layers were combined, dried over sodium sulfate and concentrated at reduced pressure to give 0.20 g of (R)-N-benzyl-3-hydroxypyrrolidine (R)-1 (quantitative yield, 95% ee).
96%	With lithium hydroxide monohydrate; water In tetrahydrofuran; methanol at 0℃; for 2h;	5.B(I) B(I). Hydrolysis of (R)-ester of formula 5 to prepare hydroxide(R)-(+)-N-benzyl 3- hydroxypyrrolidine of formula 2:The intermediate ester of formula 5 prepared above without purification (0.3 mmol) was dissolved in a mixture (10 mL) of THF and methanol (3:1), and the aqueous solution of lithium hydroxide monohydrate (O.δmmol, ImL) was added to it. The reaction mixture was stirred for 2hr at 0° C and then diluted with a saturated aqueous solution of ammonium chloride (20ml); the resulting mixture was extracted with chloroform (3x60mL). After processing and removal of the solvent and column chromatography over alumina, the yield of product of formula 2 was 96%, [α]25D +3.53(c, 2.5 CHCl3) (ee, 93%).
96%	Stage #1: (3R)-1-(phenylmethyl)pyrrolidin-3-ol Acetate With lithium hydroxide monohydrate; water In tetrahydrofuran; methanol at 0℃; for 2h; Stage #2: With ammonium chloride In tetrahydrofuran; methanol; water	5.B.I Example-5 Preparation of (R)-(+)-N-Benzyl 3-Hydroxypyrrolidine of Formula 2 A(I) : Preparation of Intermediate (R)-Ester of Formula 5A stirred solution of triphenylphosphine (41.78 mmol) in dry THF (300 mL) was maintained at 0° C. under nitrogen atmosphere. Diisopropyl azodicarboxylate (DIAD) (7.0 mL, 35.17 mmol) was added drop wise to the resulting solution at the same temperature for 15 min. Where upon it became creamy white, (-)- alcohol of molecular formula 1 (6.71 gm in 25 mL THF) was added drop wise and stirring continued for another 20 min, prior to the addition of acetic acid 70 mmol in one portion. The resulting mixture was stirred for 16 hr at room temperature. The reaction mixture was acidified with 1:1 hydrochloric acid water, aqueous layer separated from organic layer and pH of aqueous layer was adjusted to 8 by adding ammonia followed by extracted with chloroform (3×60 mL). After processing and removal of the solvent, the yield of product of the intermediate ester was 80% (6.63 g).

77%	With sodium hydroxide In methanol Ambient temperature;
14.6 g	With sodium carbonate In methanol for 4h;
98 % ee	With lithium hydroxide monohydrate In tetrahydrofuran; methanol at 0℃; for 2h;
	With water; lithium hydroxide In tetrahydrofuran

Reference： [1]Tofani, Giorgio; Petri, Antonella; Piccolo, Oreste [Tetrahedron Asymmetry, 2015, vol. 26, # 12-13, p. 638 - 643]
[2]Current Patent Assignee: COUNCIL OF SCIENTIFIC AND INDUSTRIAL RESEARCH (IN) - WO2010/58429, 2010, A1 Location in patent: Page/Page column 15
[3]Current Patent Assignee: COUNCIL OF SCIENTIFIC AND INDUSTRIAL RESEARCH (IN) - US2012/101285, 2012, A1 Location in patent: Page/Page column 5
[4]Horiguchi; Mochida [Bioscience, Biotechnology and Biochemistry, 1995, vol. 59, # 7, p. 1287 - 1290]
[5]Cesare, P. Di; Bouzard, D.; Essiz, M.; Jacquet, J. P.; Ledoussal, B.; et al. [Journal of Medicinal Chemistry, 1992, vol. 35, # 22, p. 4205 - 4213]
[6]Aga, Mushtaq A.; Kumar, Brijesh; Rouf, Abdul; Shah, Bhahwal A.; Andotra, Samar S.; Taneja, Subhash C. [Helvetica Chimica Acta, 2013, vol. 96, # 5, p. 969 - 977]
[7]Ahmad, Mudassier; Aga, Mushtaq A.; Bhat, Javeed Ahmad; Kumar, Brijesh; Rouf, Abdul; Capalash, Neena; Mintoo, Mubashir Javeed; Kumar, Ashok; Mahajan, Priya; Mondhe, Dilip Manikrao; Nargotra, Amit; Sharma, Parduman Raj; Zargar, Mohmmad Afzal; Vishwakarma, Ram A.; Shah, Bhahwal Ali; Taneja, Subhash Chandra; Hamid, Abid [Journal of Medicinal Chemistry, 2017, vol. 60, # 8, p. 3484 - 3497]

3
[ 775-15-5 ]
[ 101385-90-4 ]

Reference： [1]Journal of Medicinal Chemistry,1986,vol. 29,p. 2504 - 2511
[2]Bulletin of the Chemical Society of Japan,1996,vol. 69,p. 207 - 215
[3]Bioscience, Biotechnology and Biochemistry,1995,vol. 59,p. 1287 - 1290
[4]Tetrahedron Asymmetry,2015,vol. 26,p. 638 - 643
[5]Tetrahedron Asymmetry,2015,vol. 26,p. 638 - 643
[6]Tetrahedron Asymmetry,2015,vol. 26,p. 638 - 643
[7]Tetrahedron Asymmetry,2015,vol. 26,p. 638 - 643

4
[ 101930-07-8 ]
[ 98-59-9 ]
[ 116183-80-3 ]

Yield	Reaction Conditions	Operation in experiment
	With pyridine at 10℃; for 48h;
	In pyridine; hexane; ethyl acetate	33.A A) A) 3R-1-Benzyl-3-(p-toluenesulfonyloxy)pyrrolidine A mixture of 3R-1-benzyl-3-hydroxypyrrolidine (1 g, 5.6 mmol) and p-toluene sulfonyl chloride (1.6 g, 8.4 mmol) was stirred in pyridine (10 ml) for 4 hours. The reaction mixture was partitioned between sodium hydrogen carbonate solution and methylene chloride. The organic layer was washed with sodium hydrogen carbonate solution, followed by brine. It was then dried over sodium sulfate and concentrated first on low vacuum and finally on the high vacuum pump to remove traces of pyridine. The resultant yellow residue was flash chromatographed on a 5*25 cm SiO2 column using ethyl acetate:hexane, 1:1 as the elutant. The pure fractions were concentrated to afford 933 mg of the title A compound as a colorless oil.
	Stage #1: (R)-N-benzyl-3-hydroxypyrrolidine With n-butyllithium In tetrahydrofuran; hexanes at -78℃; for 0.0833333h; Stage #2: p-toluenesulfonyl chloride In tetrahydrofuran; hexanes at -78℃;	2 To a stirred solution of (3i?)-pyrrolidin-3-ol (2.79 g, 15.7 mmol) in THF (50 ml) at -78 0C was added nBuLi (11.2 ml of a 1.4M solution in hexanes, 15.7 mmol) giving a deep pink solution. After 5 mins, /?αra-toluenesulfonyl chloride (3.00 g, 15.7 mmol) in THF (10 ml) was added dropwise and the reaction was then raised to room temperature. The reaction was quenched with saturated aqueous NH4Cl (5 ml) and the reaction was concentrated. The residue was then dissolved in DCM (100 ml) and washed with saturated NH4CI (3 x 50 ml), dried (MgSO4), filtered and concentrated giving brown oil. This was dissolved in EtOH (25 ml) and pyrrolidine (3.95 ml, 47.0 mmol) was added. The mixture was heated in a sealed tube at 90 0C for 12 hours and then concentrated to remove excess solvent, re-dissolved in DCM (100 ml), washed with saturated aqueous NH4Cl (3 x 50 ml), dried (MgSO4), filtered and concentrated at reduced pressure. The crude material was purified on silica gel chromatography (using a gradient of eluents, 98:2:1 to 80:20:1 DCM/MeOH/NH3) to give the title compound (2.35 g, 65%) as brown oil. LCMS data: Calculated MH+ (231); Found 91% (MH+) m/z 231, Rt 4.57 mins. NMR data: 1H NMR (400 MHz, MeOD) δ ppm 7.19 - 7.37 (5 H, m), 3.54 - 3.72 (2 H, m), 2.84 - 2.98 (2 H, m), 2.72 - 2.83 (1 H, m), 2.54 (5 H, s), 2.26 - 2.41 (1 H, m), 1.96 - 2.14 (1 H, m), 1.80 (5 H, m).

With triethylamine In dichloromethane at 0 - 20℃; for 12.5h;

Reference： [1]Cesare, P. Di; Bouzard, D.; Essiz, M.; Jacquet, J. P.; Ledoussal, B.; et al. [Journal of Medicinal Chemistry, 1992, vol. 35, # 22, p. 4205 - 4213]
[2]Current Patent Assignee: BRISTOL-MYERS SQUIBB CO; VIATRIS INC - US4902684, 1990, A
[3]Current Patent Assignee: EVOTEC AG - WO2010/133544, 2010, A1 Location in patent: Page/Page column 45; 46
[4]Ahmad, Mudassier; Aga, Mushtaq A.; Bhat, Javeed Ahmad; Kumar, Brijesh; Rouf, Abdul; Capalash, Neena; Mintoo, Mubashir Javeed; Kumar, Ashok; Mahajan, Priya; Mondhe, Dilip Manikrao; Nargotra, Amit; Sharma, Parduman Raj; Zargar, Mohmmad Afzal; Vishwakarma, Ram A.; Shah, Bhahwal Ali; Taneja, Subhash Chandra; Hamid, Abid [Journal of Medicinal Chemistry, 2017, vol. 60, # 8, p. 3484 - 3497]

5
[ 101930-07-8 ]
[ 2799-21-5 ]

Yield	Reaction Conditions	Operation in experiment
98%	With hydrogen In methanol for 2h;
96%	With hydrogen In methanol at 60℃; for 72h;	2.1 Two 8 L Parr reactors were purged with nitrogen, and charged with (0.25 kg, 10 wt %) 20% PdOH/C. The system was once more purged with nitrogen and placed under vacuum. A solution of (2.50 kg, 14.1 mol) 3-hydroxypyrrolidine (1) in (15.3 L, 4.5 vol) MeOH was then charged and the system was purged with nitrogen once more. The solution was then placed under an atmosphere of hydrogen (100 psi) and warmed to 60+/-° C. and stirred for three days and was deemed complete by GC & TLC analysis (20% methanol/DCM, ninhydrin stain). The reactors were emptied and rinsed with 4 L MeOH. The reaction mixture and reactor rinses were filtered through celite and concentrated to afford 1.18 kg of 2 in 96% yield (theoretical yield=1.23 kg, GC purity=97.1%).
88%	With hydrogen In ethanol; acetic acid for 6h;

Reference： [1]Horiguchi; Mochida [Bioscience, Biotechnology and Biochemistry, 1995, vol. 59, # 7, p. 1287 - 1290]
[2]Current Patent Assignee: CYTOKINETICS INC - US2006/25470, 2006, A1 Location in patent: Page/Page column 18
[3]Naylor; Judd; Scopes; Hayes; Birch [Journal of Medicinal Chemistry, 1994, vol. 37, # 14, p. 2138 - 2144]

6
[ 156150-59-3 ]
[ 101930-07-8 ]

Yield	Reaction Conditions	Operation in experiment
64%	With lithium aluminium tetrahydride In tetrahydrofuran for 2h; Heating;

Reference： [1]Naylor; Judd; Scopes; Hayes; Birch [Journal of Medicinal Chemistry, 1994, vol. 37, # 14, p. 2138 - 2144]

7
[ 122929-12-8 ]
[ 101930-07-8 ]
[ 124445-27-8 ]

Yield	Reaction Conditions	Operation in experiment
1: 45% 2: 40%	With phosphate buffer In 1,4-dioxane at 25℃; for 24h;
1: > 99.5 % ee 2: > 99.5 % ee	With Pseudomonas fluorescens lipase AK In aq. phosphate buffer; tert-butyl methyl ether at 20℃; for 8.5h; Enzymatic reaction; enantioselective reaction;	5.1 Analytical scale enzymatic hydrolysis of rac-3-5 General procedure: The reactions were conducted at room temperature in suitable vessels, using a vortex mixer. In a typical small scale experiment, to a solution of racemic ester (10 mg) in potassium phosphate buffer (50 mM, pH 7) or in a potassium phosphate buffer/organic solvent mixture (1 mL), native (2 mg) or immobilized (200 mg) enzymes were added. The reactions were monitored by HPLC by taking samples at different intervals of time. The reaction mixture was extracted with dichloromethane (2 x 0.5 mL). The organic layer was dried over sodium sulfate, concentrated at reduced pressure and analysed by HPLC as described in Section 4.2. Data on reaction times, conversion and enantiomeric excess of the substrates and the products are presented in Tables 1-4.

Reference： [1]Tomori, Hiroshi; Shibutani, Kuniko; Ogura, Katsuyuki [Bulletin of the Chemical Society of Japan, 1996, vol. 69, # 1, p. 207 - 215]
[2]Tofani, Giorgio; Petri, Antonella; Piccolo, Oreste [Tetrahedron Asymmetry, 2015, vol. 26, # 12-13, p. 638 - 643]

8
[ 24424-99-5 ]
(R)-N-benzyl-3-hydroxypyrrolidine [ No CAS ]
[ 109431-87-0 ]

Yield	Reaction Conditions	Operation in experiment
86%	In methanol; water;	a (3R)-N-tert-Butyloxycarbonylpyrrolidin-3-ol A mixture of (3R)-N-benzylpyrrolidin-3-ol (Aldrich; 5.00 g, 28.2 mmol), di-tert-butyldicarbonate (7.39 g, 33.8 mmol), Pearlmans catalyst (0.55 g), methanol (200 ml) and water (20 ml) were hydrogenated at 40 psi in a Parr apparatus for 2 h. The catalyst was removed by filtration through celite and the solvents removed under vacuum. The crude product was chromatographed on silica gel eluding with ethyl acetate/hexane (1:1) to give the title-pyrrolidinol (4.55 g, 86%), δ (250 MHz, CDCl3) 1.46 (9H, s, OC(Me)3), 1.87-2.03 (2H, m, CH2),2.07 (1H, s, OH), 3.33-3.50 (4H, m, 2 of CH2), 4.42-4.48 (1H, m,CH--OH).

Reference： [1]Journal of Medicinal Chemistry,1999,vol. 42,p. 677 - 690
[2]Patent: US5854268,1998,A
[3]Journal of Medicinal Chemistry,1997,vol. 40,p. 3497 - 3500

9
[ 101930-07-8 ]
[ 204972-99-6 ]

Yield	Reaction Conditions	Operation in experiment
82%	With (bis-(2-methoxyethyl)amino)sulfur trufluoride In dichloromethane at 20℃; for 15h;

Reference： [1]Singh, Rajendra P.; Shreeve, Jean'ne M. [Journal of Fluorine Chemistry, 2002, vol. 116, # 1, p. 23 - 26]

10
[ 5586-15-2 ]
[ 101930-07-8 ]
[ CAS Unavailable ]

Yield	Reaction Conditions	Operation in experiment
90%	With tributylphosphine In benzene at 80℃; for 72h;

Reference： [1]Siedlecka, Renata; Wojaczynska, Elzbieta; Skarzewski, Jacek [Tetrahedron Asymmetry, 2004, vol. 15, # 9, p. 1437 - 1444]

11
[ 101930-07-8 ]
[ 882-33-7 ]
[ 722545-11-1 ]

Yield	Reaction Conditions	Operation in experiment
90%	With tributylphosphine In benzene at 80℃; for 72h;

Reference： [1]Siedlecka, Renata; Wojaczynska, Elzbieta; Skarzewski, Jacek [Tetrahedron Asymmetry, 2004, vol. 15, # 9, p. 1437 - 1444]

12
[ 2179-79-5 ]
[ 101930-07-8 ]
[ 933773-77-4 ]

Yield	Reaction Conditions	Operation in experiment
63%	With tributylphosphine In toluene at 0 - 20℃;

Reference： [1]Zielinska-Blajet, Mariola; Siedlecka, Renata; Skarzewski, Jacek [Tetrahedron Asymmetry, 2007, vol. 18, # 1, p. 131 - 136]

13
[ 101930-07-8 ]
[ 114636-29-2 ]

Yield	Reaction Conditions	Operation in experiment
	Multi-step reaction with 2 steps 1: 96.7 percent / Et₃N / tetrahydrofuran / 4 h / -10 - 0 °C 2: NaN₃ / dimethylformamide / 80 °C
	Multi-step reaction with 2 steps 1: 84 percent / triethylamine / CH₂Cl₂ / 1.) 0 deg C, 20 min, 2.) room temperature, 1.5 h 2: 87 percent / tetra-n-butylammonium azide / acetonitrile / 1 h / 65 °C
	Multi-step reaction with 2 steps 1: pyridine / 48 h / 10 °C 2: NaN₃ / dimethylformamide / 7 h / 60 °C

Multi-step reaction with 2 steps 1: triethylamine / dichloromethane / 12.5 h / 0 - 20 °C 2: sodium azide; tetrabutylammomium bromide / N,N-dimethyl-formamide / 6 h / 60 °C

Reference： [1]Huang; Luedtke; Freeman; Wu; Mach [Journal of Medicinal Chemistry, 2001, vol. 44, # 11, p. 1815 - 1826]
[2]Rosen, Terry; Chu, Daniel T. W.; Lico, Isabella M.; Fernandes, Prabhavathi B.; Shen, Linus; et al. [Journal of Medicinal Chemistry, 1988, vol. 31, # 8, p. 1586 - 1590]
[3]Cesare, P. Di; Bouzard, D.; Essiz, M.; Jacquet, J. P.; Ledoussal, B.; et al. [Journal of Medicinal Chemistry, 1992, vol. 35, # 22, p. 4205 - 4213]
[4]Ahmad, Mudassier; Aga, Mushtaq A.; Bhat, Javeed Ahmad; Kumar, Brijesh; Rouf, Abdul; Capalash, Neena; Mintoo, Mubashir Javeed; Kumar, Ashok; Mahajan, Priya; Mondhe, Dilip Manikrao; Nargotra, Amit; Sharma, Parduman Raj; Zargar, Mohmmad Afzal; Vishwakarma, Ram A.; Shah, Bhahwal Ali; Taneja, Subhash Chandra; Hamid, Abid [Journal of Medicinal Chemistry, 2017, vol. 60, # 8, p. 3484 - 3497]

14
[ 101930-07-8 ]
[ 114715-38-7 ]

Yield	Reaction Conditions	Operation in experiment
	Multi-step reaction with 3 steps 1: 96.7 percent / Et₃N / tetrahydrofuran / 4 h / -10 - 0 °C 2: NaN₃ / dimethylformamide / 80 °C 3: LiAlH₄ / tetrahydrofuran / 6 h / Heating
	Multi-step reaction with 3 steps 1: 84 percent / triethylamine / CH₂Cl₂ / 1.) 0 deg C, 20 min, 2.) room temperature, 1.5 h 2: 87 percent / tetra-n-butylammonium azide / acetonitrile / 1 h / 65 °C 3: hydrogen / 5percent Pt/C / methanol / 4 h / 3040 Torr
	Multi-step reaction with 3 steps 1: triethylamine / dichloromethane / 12.5 h / 0 - 20 °C 2: sodium azide; tetrabutylammomium bromide / N,N-dimethyl-formamide / 6 h / 60 °C 3: triphenylphosphine / N,N-dimethyl-formamide / 20 °C

Reference： [1]Huang; Luedtke; Freeman; Wu; Mach [Journal of Medicinal Chemistry, 2001, vol. 44, # 11, p. 1815 - 1826]
[2]Rosen, Terry; Chu, Daniel T. W.; Lico, Isabella M.; Fernandes, Prabhavathi B.; Shen, Linus; et al. [Journal of Medicinal Chemistry, 1988, vol. 31, # 8, p. 1586 - 1590]
[3]Ahmad, Mudassier; Aga, Mushtaq A.; Bhat, Javeed Ahmad; Kumar, Brijesh; Rouf, Abdul; Capalash, Neena; Mintoo, Mubashir Javeed; Kumar, Ashok; Mahajan, Priya; Mondhe, Dilip Manikrao; Nargotra, Amit; Sharma, Parduman Raj; Zargar, Mohmmad Afzal; Vishwakarma, Ram A.; Shah, Bhahwal Ali; Taneja, Subhash Chandra; Hamid, Abid [Journal of Medicinal Chemistry, 2017, vol. 60, # 8, p. 3484 - 3497]

15
[ 101930-07-8 ]
[ 707539-75-1 ]

Yield	Reaction Conditions	Operation in experiment
	Multi-step reaction with 6 steps 1: 96.7 percent / Et₃N / tetrahydrofuran / 4 h / -10 - 0 °C 2: NaN₃ / dimethylformamide / 80 °C 3: LiAlH₄ / tetrahydrofuran / 6 h / Heating 4: 77 percent / CH₂Cl₂ / 20 °C 5: H₂ / 5percent Pd/C / methanol / 12 h / 2585.81 Torr 6: CF₃COOH / CH₂Cl₂ / 1 h / 20 °C

Reference： [1]Huang; Luedtke; Freeman; Wu; Mach [Journal of Medicinal Chemistry, 2001, vol. 44, # 11, p. 1815 - 1826]

16
[ 101930-07-8 ]
[ 1026904-33-5 ]

Yield	Reaction Conditions	Operation in experiment
	Multi-step reaction with 5 steps 1: 96.7 percent / Et₃N / tetrahydrofuran / 4 h / -10 - 0 °C 2: NaN₃ / dimethylformamide / 80 °C 3: LiAlH₄ / tetrahydrofuran / 6 h / Heating 4: 77 percent / CH₂Cl₂ / 20 °C 5: H₂ / 5percent Pd/C / methanol / 12 h / 2585.81 Torr

Reference： [1]Huang; Luedtke; Freeman; Wu; Mach [Journal of Medicinal Chemistry, 2001, vol. 44, # 11, p. 1815 - 1826]

17
[ 101930-07-8 ]
[ 342876-59-9 ]

Yield	Reaction Conditions	Operation in experiment
	Multi-step reaction with 7 steps 1: 96.7 percent / Et₃N / tetrahydrofuran / 4 h / -10 - 0 °C 2: NaN₃ / dimethylformamide / 80 °C 3: LiAlH₄ / tetrahydrofuran / 6 h / Heating 4: 77 percent / CH₂Cl₂ / 20 °C 5: H₂ / 5percent Pd/C / methanol / 12 h / 2585.81 Torr 6: CF₃COOH / CH₂Cl₂ / 1 h / 20 °C 7: Et₃N / CH₂Cl₂ / 20 °C

Reference： [1]Huang; Luedtke; Freeman; Wu; Mach [Journal of Medicinal Chemistry, 2001, vol. 44, # 11, p. 1815 - 1826]

18
[ 101930-07-8 ]
[ 127423-61-4 ]

Yield	Reaction Conditions	Operation in experiment
	Multi-step reaction with 2 steps 1: 86 percent / H₂ / Pearlmans catalyst / methanol; H₂O / 2 h / 2068.59 Torr 2: Et₃N / CH₂Cl₂ / 16 h / Ambient temperature
	Multi-step reaction with 2 steps 1: H₂ / Pd(OH)2 / methanol; H₂O 2: Et₃N / CH₂Cl₂

Reference： [1]Sternfeld, Francine; Guiblin, Alexander R.; Jelley, Richard A.; Matassa, Victor G.; Reeve, Austin J.; Hunt, Peter A.; Beer, Margaret S.; Heald, Anne; Stanton, Josephine A.; Sohal, Bindi; Watt, Alan P.; Street, Leslie J. [Journal of Medicinal Chemistry, 1999, vol. 42, # 4, p. 677 - 690]
[2]Castro; Street; Guiblin; Jelley; Russell; Sternfeld; Beer; Stanton; Matassa [Journal of Medicinal Chemistry, 1997, vol. 40, # 22, p. 3497 - 3500]

19
[ 101930-07-8 ]
[ 177947-67-0 ]

Yield	Reaction Conditions	Operation in experiment
	Multi-step reaction with 2 steps 1: 86 percent / H₂ / Pearlmans catalyst / methanol; H₂O / 2 h / 2068.59 Torr 2: 1.) NaH / 1.) THF, 0 deg C, 0.3 h, 2.) THF, RT, 18 h
	Multi-step reaction with 2 steps 1: H₂ / Pd(OH)2 / methanol; H₂O 2: NaH / tetrahydrofuran

20
[ 101930-07-8 ]
[ 199336-82-8 ]

Yield	Reaction Conditions	Operation in experiment
	Multi-step reaction with 3 steps 1: H₂ / Pd(OH)2 / methanol; H₂O 2: Et₃N / CH₂Cl₂ 3: toluene / 90 °C

Reference： [1]Castro; Street; Guiblin; Jelley; Russell; Sternfeld; Beer; Stanton; Matassa [Journal of Medicinal Chemistry, 1997, vol. 40, # 22, p. 3497 - 3500]

21
[ 101385-90-4 ]
[ 101385-90-4 ]

Reference： [1]Bioscience, Biotechnology and Biochemistry,1995,vol. 59,p. 1287 - 1290
[2]Bioscience, Biotechnology and Biochemistry,1995,vol. 59,p. 1287 - 1290
[3]Journal of Medicinal Chemistry,1992,vol. 35,p. 4205 - 4213
[4]Helvetica Chimica Acta,2013,vol. 96,p. 969 - 977
[5]Tetrahedron Asymmetry,2015,vol. 26,p. 638 - 643
[6]Journal of Medicinal Chemistry,2017,vol. 60,p. 3484 - 3497

22
[ 101930-07-8 ]
[ 114715-39-8 ]

Yield	Reaction Conditions	Operation in experiment
	Multi-step reaction with 3 steps 1: 84 percent / triethylamine / CH₂Cl₂ / 1.) 0 deg C, 20 min, 2.) room temperature, 1.5 h 2: 87 percent / tetra-n-butylammonium azide / acetonitrile / 1 h / 65 °C 3: hydrogen / 5percent Pt/C / methanol / 4 h / 3040 Torr

Reference： [1]Rosen, Terry; Chu, Daniel T. W.; Lico, Isabella M.; Fernandes, Prabhavathi B.; Shen, Linus; et al. [Journal of Medicinal Chemistry, 1988, vol. 31, # 8, p. 1586 - 1590]

23
[ 101930-07-8 ]
[ 58479-61-1 ]
[ 365997-69-9 ]

Yield	Reaction Conditions	Operation in experiment
	With 1H-imidazole In DMF (N,N-dimethyl-formamide) at 0 - 20℃; for 216h;	58 (3R)-1-Benzyl-3-hydroxypyrrolidine (500 µL) and imidazole (466 mg) were dissolved in N,N-dimethylformamide (15 mL), and tert-butyldiphenylsilyl chloride (1.57 mL) was added to the solution under ice cooling, followed by stirring at room temperature for 9 days. The solvent was distilled away under reduced pressure, and the residue was partitioned by adding methylene chloride and water. The organic layer was dried over sodium sulfate anhydrate, and the solvent was distilled away under reduced pressure. The residue was subjected to silica gel flash column chromatography (hexane : ethyl acetate = 3:1), to thereby give the title compound (1.27 g).1H-NMR(CDCl3) δ:1.05(9H, s), 1.70-1.85(1H, m), 1.90-2.00(1H, m), 2.45-2.65(3H, m), 2.70-2.80(1H, m), 3.50-3.70(2H, m), 4.35-4.45(1H, m), 7.20-7.45(11H, m), 7.60-7.70(4H, m). MS(ESI)m/z:416(M+H)+.
	With 1H-imidazole In DMF (N,N-dimethyl-formamide) at 0 - 20℃; for 216h;	58 (3R)-1-Benzyl-3-(tert-butyldiphenylsilyloxy)pyrrolidine: [Referential Example 58] (3R)-1-Benzyl-3-(tert-butyldiphenylsilyloxy)pyrrolidine: (3R)-1-Benzyl-3-hydroxypyrrolidine (500 μl) and imidazole (466 mg) were dissolved in N,N-dimethylformamide (15 ml), tert-butyldiphenylsilyl chloride (1.57 ml) was added under ice cooling, and the mixture was stirred at room temperature for 9 days.. After the solvent was distilled off under reduced pressure, and methylene chloride and water were added to the residue to conduct liquid separation, the resultant organic layer was dried over anhydrous sodium sulfate, and the solvent was distilled off under reduced pressure.. The residue was subjected to flash column chromatography on silica gel (hexane:ethyl acetate = 3:1) to obtain the title compound (1.27 g).1H-NMR (CDCl3) δ: 1.05(9H,s), 1.70-1.85(1H,m), 1.90-2.00(1H,m), 2.45-2.65(3H,m), 2.70-2.80(1H,m), 3.50-3.70(2H,m), 4.35-4.45(1H,m), 7.20-7.45(11H,m), 7.60-7.70(4H,m). MS (ESI) m/z: 416(M+H)+.

Reference： [1]Current Patent Assignee: DAIICHI SANKYO COMPANY, LIMITED - EP1577301, 2005, A1 Location in patent: Page/Page column 96
[2]Current Patent Assignee: DAIICHI SANKYO COMPANY, LIMITED - EP1405852, 2004, A1 Location in patent: Page 88

24
[ 100-44-7 ]
[ 101930-07-8 ]

Yield	Reaction Conditions	Operation in experiment
44.4%	Stage #1: (R)-3-hydroxypyrrolidine hydrochloride With triethylamine In dichloromethane at 20℃; for 0.0833333h; Stage #2: benzyl chloride In dichloromethane at 20℃; for 15h; Heating / reflux; Stage #3: With sodium hydroxide In dichloromethane; chloroform; water for 0.166667h;	1.2 Step 2: Preparation of (3R)-1-benzyl-pyrrolidin-3-ol The compound (3R) -pyrrolidin-3-ol hydrochloride (2.2 g, 17.8 MM) was dissolved in dichloromethane (25.0 ml) and triethylamine (5.0 ml, 35.6 mM) was added at room temperature with constant stirring for 5 minutes. Benzyl chloride (2.5 ml, 21.4 MM) was added to it in one lot at the same temperature followed by refluxing for 15 hours. The reaction mixture was diluted with chloroform and 1N sodium hydroxide (15.0 ml) was added with constant stirring for 10 minutes. The organic layer was separated and washed with aqueous sodium bicarbonate and brine solution. It was further dried over anhydrous sodium sulphate and concentrated to get the title compound. Yield = 44.4% (1.4 g, 7.9 mM). 1H NMR (CDC13) : δ 7.31-7.37 (M, 5H), 4.36-4.37 (M, 1H), 3.68 (s, 1H), 2.73-2.92 (M, 1H), 2.72 (d, J = 10 Hz, 1H), 2.56-2.61 (M, 1H), 2.20-2.37 (M, 2H), 1.77-1.81 (M, 1H)

Reference： [1]Current Patent Assignee: SUN PHARMACEUTICAL INDUSTRIES LIMITED - WO2004/56767, 2004, A1 Location in patent: Page 14

25
[ 101385-90-4 ]
[ 427-49-6 ]
[ 719278-61-2 ]

Yield	Reaction Conditions	Operation in experiment
91%	With triphenylphosphine; In tetrahydrofuran; at 20℃; for 20h;	The compound <strong>[427-49-6]2-cyclopentyl-2-hydroxy-2-phenylacetic acid</strong> (0.3 g, 1.36 mM), (3R)-1- benzyl-pyrrolidin-3-ol (0.2 g, 1.14 mM) and triphenylphosphine (0.36 g, 1.36 MM) were dissolved in dry tetrahydrofuran (10.0 ml). To this, a solution of DIETHYLAZABICYCLOCARBOXYLATE (0.2 ml, 1.36 mM) in dry tetrahydrofuran (2.0 ml) was added dropwise under nitrogen atmosphere at room temperature with constant stirring and the stirring was continued for 20 hours. Tetrahydrofuran was evaporated under vacuum and the residue was taken in chloroform and washed with saturated sodium bicarbonate solution, water and brine solution followed by drying and concentrating over anhydrous sodium sulphate. The residue was purified by silica gel column chromatography using 30% ethyl acetate in hexane to get the title compound as oil. Yield = 91% (0.39 g, 1.03 MM). 1H NMR (CDCl3) : delta 7.64-7.67 (M, 2H), 7.26-7.35 (M, 8H), 5.17-5.23 (M, 1H), 3.56-3.74 (M, 3H), 2.75-2.90 (M, 4H), 2.00-2.52 (M, 3H, including-OH), 1.29-2.00 (M, 8H).

Reference： [1]Patent: WO2004/56767,2004,A1 .Location in patent: Page 17-18

26
[ 101930-07-8 ]
[ 64471-45-0 ]
[ 719278-73-6 ]

Yield	Reaction Conditions	Operation in experiment
23%	With di-isopropyl azodicarboxylate; triphenylphosphine In tetrahydrofuran at 20℃; for 20h;	15 Example 15; Preparation of (3S)-1-benzyl-pyrrolidin-3-yl-(2R)-cyclopentyl(hydroxy)phenyl acetate (Compound No. 15) The compounds (2R) -hydroxy (3-oxocyclopentyl) -2-hydroxy-2-phenylacetic acid (3.0 g, 13.6 mM), (3R)-l-benzyl-pyrrolidin-3-ol (2.0 g, 11.4 mM) were dissolved in dry tetrahydrofuran (80. 0ml) and triphenylphosphine (3.6 mM). To the reaction mixture, a solution of diisopropyl azadicarboxylate (2.7 ml, 13.6 mM) in dry tetrahydrofuran (20.0 ml) was added dropwise under nitrogen atmosphere at room temperature with constant stirring and the stirring was continued for 20 hours at room temperature. Tetrahydrofuran was evaporated under vacuum and the residue was taken in chloroform and washed with saturated sodium bicarbonate solution, water and brine solution, dried over anhydrous sodium sulphate and concentrated. The residue was purified by silica gel column chromatography using 15% ethyl acetate in hexane to get the title compound. Yield = 23% (1. 2 G, 3. 17 MM). 1H NMR (CDCl3): δ 7.65-7.67 (M, 2H), 7.26-7.36 (M, 8H), 5.16-5.21 (M, 1H), 3.56-3.75 (M, 3H), 2.70-2.81 (M, 4H), 2.50-2.60 (M, 1H), 2.10-2.30 (M, 1H), 1.26-1.90 (M, 9H).

Reference： [1]Current Patent Assignee: SUN PHARMACEUTICAL INDUSTRIES LIMITED - WO2004/56767, 2004, A1 Location in patent: Page 24-25

27
[ 719278-78-1 ]
[ 101930-07-8 ]
[ 719278-67-8 ]

Yield	Reaction Conditions	Operation in experiment
11%	With triphenylphosphine; diethylazodicarboxylate In tetrahydrofuran at 20℃; for 20h;	9 Example 9; Preparation of (3S)-1-benzylpyrrolidin-3-yl(2R)-hydroxy(3-oxocyclopentyl)phenyl acetate (Compound No. 9) The compounds (2R)-hydroxy (3-oxocyclopentyl) phenylacetic acid (1.0 g, 4.27 MM), (3R)-l-benzyl-pyrrolidin-3-ol (0.63 g, 3.56 mM) were dissolved in dry tetrahydrofuran (30ml) and triphenylphosphine (1.12 g, 4.27 mM). To the reaction mixture, a solution of DIETHYLAZOLDICARBOXYATE (0.7 ml, 4.27 mM) in dry tetrahydrofuran (4.0 ml) was added dropwise under nitrogen atmosphere at room temperature with constant stirring and stirring was continued for 20 hours at the same temperature. Tetrahydrofuran was evaporated under vacuum and the residue was purified by silica gel column chromatography using 35% ethyl acetate in hexane to get the title compound. Yield = 11% (0. 18 g, 0. 46 mM). 1H NMR (CDCl3) : δ 7.61-7.67 (M, 2H), 7.30-7.40 (M, 8H), 5.18-5.23 (M, 1H), 3.88 (brs, - OH), 3.57-3.70 (M, 2H), 3.21 (M, 1H), 2.68-2.80 (M, 3H), 2.39-2.44 (M, 1H), 2.12-2.27 (M, 4H), 1.61-1.81 (M, 4H).

Reference： [1]Current Patent Assignee: SUN PHARMACEUTICAL INDUSTRIES LIMITED - WO2004/56767, 2004, A1 Location in patent: Page 21

28
[ 90-97-1 ]
[ 101930-07-8 ]
[ 791119-33-0 ]

Yield	Reaction Conditions	Operation in experiment
67%	With toluene-4-sulfonic acid In toluene Heating / reflux;	Preparation of (R)-1-benzyl-3-(4,4'-dichlorobenzhydryloxy)pyrrolidine (73) A solution of (R)- (+)-L-BENZYL-3-PYRROLIDINOL (55 mmol), 4,4'-dichlorobenzhyrdol (113 mmol) and p-toluenesulphonic acid (113 mmol) in toluene (150 mL) was heated to reflux in a Dean-Stark apparatus overnight. The solution was cooled, washed with 10% sodium hydroxide solution, dried (MGS04) and concentrated in vacuo. The residue was purified by flash column chromatography [SI02 ; ISOHEXANE No. ethyl acetate-isohexane (1: 4) ] to furnish the product as a brown oil (15.1 g, 67%). NMR (400MHZ, -DMSO) §H 1.75 (1H, m), 2.00 (1H, m), 2. 38 (1H, m), 2.53 (1H, m), 2.60 (2H, m), 3. 55 (2H, m), 4.00 (1H, m), 5. 51 (1H, s), 7. 21-7. 42 (13H, m) LC (50/80) 98.7%, 8.20 min

Reference： [1]Current Patent Assignee: LIGAND PHARMACEUTICALS INC - WO2004/96794, 2004, A1 Location in patent: Page 46

29
[ 24985-85-1 ]
[ 101385-90-4 ]
[ 872030-39-2 ]

Yield	Reaction Conditions	Operation in experiment
49%	With tributylphosphine; 1,1'-azodicarbonyl-dipiperidine; at 0 - 20℃;	To a cold (0 C.) mixture of ethyl-5-hydroxyindole-2-carboxylate (purchased at Biosynth, H-6350, 20.5 g, 1.0 eq.), (R)-1-benzyl-3-pyrrolidinol (23 g, 1.3 eq.) and tri-n-butylphosphine (58 mL, 2.0 eq.) was slowly added 1,1'-(azodicarbonyl)dipiperidine (50.4 g, 2.0 eq.) in several portions. The reaction mixture was stirred at room temperature overnight and then filtered off. The filtrate was concentrated in vacuo and diethylether was added. The precipitate was filtered off and the filtrate was concentrated in vacuo and purified on silica eluding with dichloromethane/methanol/ammoniac. One fraction was isolated and dried in vacuo, to yield 18 mg (49%) of the desired product as light yellow foam. MS (m/e): 365.5 (MH+, 100%).
	With tributylphosphine; 1,1'-azodicarbonyl-dipiperidine; In tetrahydrofuran; at 20℃; for 17h;	Example 135; J 5-( (S)-l- Isopropyl-pyrrolidin-3-yloxy)-lH -indol-2-yll-morphotin-4-yl-methanone; a) Step 1: 5-((S)-l-Benzyl-pyrrolidin-3-yloxy)-lH-indole-2-carboxylic acid ethyl ester; A mixture of 20.5 g (0.1 mol) ethyl-5-hydroxyindole-2-carboxylate, 23 g ( 0.13 mol) (R)-l-benzyl-pyrrolidine, 58 ml (0.2 mol) tri-n-butyl-phosphine and 50 g (0.2 mol) 1,1'- azodicarbonyl dipiperidine in 600 ml THF was stirred for 17 h at room temperature. The suspension was filtered and the filtrate was evaporated to dryness. The residue was taken up in 100 ml heptane/DCM 1/1 and the precipitate was filtered off and washed with 100 ml heptane/DCM 1/1. The filtrate was evaporated to dryness and the residue was taken up in 100 ml DCM and purified by flash column chromatography on silica eluting with a gradient of ethyl acetate/ heptane 1/3 to 2/1. The product containing fractions were pooled and evaporated to dryness and again purified on silica eluting with a gradient from DCM/ 2N NH3 in MeOH 99/1 to 19/1. 6.2g of pure product were obtained from pooling and evaporation of pure fractions. This was recrystallised from diethyl ether and heptane and washed with diethyl ether/ heptane to yield 3.5 g of pure product MS (m/e): 365.1 (MH+, 100%). 26 g of impure product were obtained from pooling and evaporation of the respective fractions. This was recrystallised from diethyl ether and heptane and washed with diethyl ether/ heptane to yield 9.0 g of pure product. All filtrates were pooled and evaporated to dryness to yield 14 g of slightly impure product which was used without further purification in the consecutive steps.

Reference： [1]Patent: US2007/123526,2007,A1 .Location in patent: Page/Page column 14
[2]Patent: WO2005/123716,2005,A1 .Location in patent: Page/Page column 73

30
[ 104706-47-0 ]
[ 100-44-7 ]
[ 101930-07-8 ]

Yield	Reaction Conditions	Operation in experiment
	Stage #1: (R)-3-hydroxypyrrolidine hydrochloride; benzyl chloride With triethylamine In dichloromethane at 20℃; for 0.0833333 - 15h; Heating / reflux; Stage #2: With sodium hydroxide In chloroform; water for 0.166667h;	2 Step a: Preparation of (3R)-l-benzyl-pyrrolidin-3-olThe compound (3R)-pyrrolidin-3-ol hydrochloride (2.2 g, 17.8 mM) was dissolved in dichloromethane (25.0 ml) and triethylamine (5.0 ml, 35.6 mM) was added at room temperature with constant stirring for about 5 minutes. Benzyl chloride (2.5 ml, 21.4 mM) was added to it in one lot at the same temperature followed by refluxing for about 15 hours. The reaction mixture was diluted with chloroform and IN sodium hydroxide (15.0 ml) was added with constant stirring for about 10 minutes. The organic layer was separated and washed with aqueous sodium bicarbonate and brine solution. It was further dried over anhydrous sodium sulphate and concentrated to get the title compound.

Reference： [1]Current Patent Assignee: SUN PHARMACEUTICAL INDUSTRIES LIMITED - WO2006/18708, 2006, A2 Location in patent: Page/Page column 25

31
[ 101930-07-8 ]
[ 603-35-0 ]
[ 1972-28-7 ]
[ 128510-52-1 ]

Yield	Reaction Conditions	Operation in experiment
	With hydrogenchloride; benzoic acid In tetrahydrofuran; hexane; ethyl acetate	34.A A) A) 3S-1-Benzyl-3-(benzoyloxy)-pyrrolidine Diethyl azodicarboxylate (4.8 ml; 30 mmol) was added dropwise to a stirred solution of 3(R)-1-benzyl-3-hydroxypyrrolidine (3.5 g, 20 mmol), triphenyl phosphine (7.86 g, 30 mmol), and benzoic acid (6.12 g, 50 mmol) in 200 ml of tetrahydrofuran at room temperature. After stirring for 1.5 hours, the tetrahydrofuran was removed in vacuo and the residue was partitioned between 1N hydrochloric acid and ethyl acetate. The ethyl acetate layer was extracted again with 1N hydrochloric acid and the combined acid layers were basified with solid sodium carbonate. The resulting basic layer was extracted with ethyl acetate. The ethyl acetate layer was washed with water, followed by brine and then dried over sodium sulfate. The organic layer was concentrated and the residue was flash chromatographed on a 5*30 cm SiO2 column using ethyl acetate/hexane, 1:3 as the mobile phase. The pure fractions were concentrated to afford 3.30 g (59%) yield of the title A compound as a colorless oil.

Reference： [1]Current Patent Assignee: BRISTOL-MYERS SQUIBB CO; VIATRIS INC - US4902684, 1990, A

32
[ 101930-07-8 ]
[ 204973-04-6 ]

Yield	Reaction Conditions	Operation in experiment
706 mg(72%)	With triphenylphosphine In tetrachloromethane; water	35 (S)-1-Benzyl-3-chloropyrrolidine Preparation 35 (S)-1-Benzyl-3-chloropyrrolidine To a stirred solution of (R)-1-benzyl-3-pyrrolidinol (886 mg, 5.0 mmol) in CCl4(20 ml) was added triphenylphosphine(1.574 g, 6.0 mmol) at rt. After 20 h stirring at reflux temperature, the solvent was evapolated. Saturated NaHCO3 aqueous solution and water was added to the residue, and the mixture was extracted with AcOEt. The extract was brine, dried(Na2SO4), and concentrated to give brown oil, which was purified by column chromatography (silica gel; 100 g, CH2Cl2/MeOH: 50/1-45/1) to give 706 mg(72%) of pale yellow oil. 1H NMR (270 MHz, CDCl3) δ 7.33-7.23(5H, m), 4.42-4.33(1H, m), 3.73-3.61(2H, m) 3.09(1H, dd, J=6.6, 10.6 Hz), 2.81-2.61(3H, m), 2.48-2.35(1H, m), 2.13-2.03(1H, m).

Reference： [1]Current Patent Assignee: PFIZER INC - US6201007, 2001, B1

33
[ 1268163-54-7 ]
[ 101930-07-8 ]

Yield	Reaction Conditions	Operation in experiment
	Stage #1: (R)-1-benzyl-3-(tert-butyldimethylsilyloxy)pyrrolidine With hydrogenchloride; methanol; water at 0℃; for 3h; Stage #2: With sodium hydroxide In methanol for 7h;	10 Example 10: Preparation of (R )- N -benzyl-3-hydroxypyrrolidine [91] To 2 L high-pressure reactor, 100 g of (R)-2-(t - butyldimethylsilyloxy)-3-chloropropionitrile dissolved into methanol (500 mL) and 25 g of Raney-Ni suspended in methanol (500 mL) were added. The mixture was heated to 1000C and stirred for 2 hours under 5 bar of hydrogen pressure. The reaction solution was cooled to room temperature and filtered through celite to remove the catalyst. 34.2 g of NaOH and 65.0 g of benzyl chloride were successively added dropwise to the remaining filtrate. After stirring for 5 hours, the reaction mixture was concentrated under reduced pressure, and then water (300 mL) and ethyl acetate (450 mL) were added to the residue. After stirring for 30 minutes, the organic layer was concentrated under reduced pressure and the residue was dissolved in methanol (200 mL). Concentrated aqueous hydrochloric acid (37.1 mL) was slowly added dropwise at O0C to the resultant solution. After stirring for 3 hours, 10 % NaOH methanolic solution (179.6 g) was added dropwise. The resultant precipitate was filtered off and the filtrate was concentrated under reduced pressure. After adding water (300 mL) and ethyl acetate (450 mL), the organic layer was separated. The aqueous layer was extracted twice using ethyl acetate (300 mL). The collected organic layer was dried with anhydrous magnesium sulfate, filtered and concentrated under reduced pressure. The resultant residue was distillated under reduced pressure to obtain 66.0 g of the targeted compound (/?)-N-benzyl-3-hydroxypyrrolidine (yield: 87 %).[92] 1U NMR (CDCl , 300 MHz): δ 1.75(m, IH), 2.21(m, IH), 2.34(m, IH), 2.50(bs,IH), 2.60(m, IH), 2.7 l(m, IH), 2.89(m, IH), 3.71(s, 2H), 4.3 l(m, IH), 7.29(S, 2H) ppm.

Reference： [1]Current Patent Assignee: RS TECH - WO2007/24113, 2007, A1 Location in patent: Page/Page column 18-19

34
[ 1104643-29-9 ]
[ 101930-07-8 ]

Yield	Reaction Conditions	Operation in experiment
99.33 % ee	With hydrogenchloride In water; 1,2-dichloro-ethane at 20 - 60℃; for 4h;	14 304 g of R-3-t-butoxy-N-benzylpyrrolidine thus obtained was added to dichloroethane 581 mL. Thereafter, concentrated HCl 252 g (2.486 mol) was dropwisely added to the solution for 2 hour. The solution was stirred for 2 hours at 55-600C. The reaction mixture was cooled to room temperature and then water 100 g was added to the mixture. Organic layer was removed. To the water layer, dichloroethane 294 mL was added and then NaOH 109.4 g (2.734 mol) was added for 1 hour and stirred at room temperature for 2 hours. After separation, Na2SO4 30 g was added to the organic solution and stirred for 30 minutes. Solid phase inorganic material was filtered out. Concentration under reduced pressure gave 165.1 g of R- 1 -benzyl- 3 -pyrrolidinol (overall two step yield 71%, chemical purity 99.26%, optical purity 99.33%ee).

Reference： [1]Current Patent Assignee: RS TECH - WO2009/11551, 2009, A2 Location in patent: Page/Page column 17

35
[ 921202-52-0 ]
[ 921202-64-4 ]
[ 101930-07-8 ]

Yield	Reaction Conditions	Operation in experiment
1: 68% 2: 3%	Stage #1: (2S,3R)-1-benzyl-2-vinylpyrrolidin-3-ol With hydrogenchloride In methanol at 0℃; for 0.5h; Inert atmosphere; Stage #2: With ozone In methanol at -78℃; Stage #3: With sodium tetrahydroborate In methanol at -78 - -10℃; Inert atmosphere;

Reference： [1]Location in patent: experimental part Rives, Arnaud; Genisson, Yves; Faugeroux, Vanessa; Zedde, Chantal; Lepetit, Christine; Chauvin, Remi; Saffon, Nathalie; Andrieu-Abadie, Nathalie; Colie, Sandra; Levade, Thierry; Baltas, Michel [European Journal of Organic Chemistry, 2009, # 15, p. 2474 - 2489]

36
[ 101385-90-4 ]
[ 88196-70-7 ]
[ 870859-01-1 ]

Yield	Reaction Conditions	Operation in experiment
		(1) To a solution of 8.0 g of (R)-1-benzyl-3-pyrrolidinol and 16.5 ml of diisopropylethylamine dissolved in 400 ml of methylene chloride was added dropwise a solution of 13.4 g of anhydrous trifluoromethanesulfonic acid in 50 ml of a methylene chloride at -20C or lower. The reaction mixture was stirred for 15 minutes while maintaining it to -20C, then, a solution of 9.88 g of (R)-1-(3-methoxyphenyl)-ethylamine in 100 ml of methylene chloride was added dropwise to the mixture at -20C or lower, and the reaction mixture was stirred at room temperature for 16 hours. To the reaction mixture were added a saturated aqueous sodium bicarbonate solution and chloroform, the mixture was stirred and the liquids were separated. The organic layer was dried and concentrated, and the residue was purified by silica gel column chromatography (chloroform:methanol=1:0? 50:1) and NH silica gel column chromatography (hexane:ethyl acetate=25:1?10:1) to obtain 3.98 g of (S)-(1-benzyl-pyrrolidin-3-yl)-[(R)-1-(3-methoxyphenyl)ethyl]amine. MS · APCI (m/z): 311 [M+H] +

Reference： [1]Patent: EP1757582,2007,A1 .Location in patent: Page/Page column 32

37
[ 108-24-7 ]
[ 101930-07-8 ]
[ 116143-02-3 ]

Yield	Reaction Conditions	Operation in experiment
63%	With pyridine at 20℃; for 23h;	General procedure: (3R)-1-benzyl-3-hydroxypyrrolidine-2,5-dione 1 (300 mg, 1.5 mmol) was dissolved in pyridine (0.78 mL) and acetic anhydride (1.23 mL) was then added. The solution was stirred for 23 h at rt. The solvents were removed in vacuo, and the crude product was purified by silica gel column chromatography [(2:1) to (1:1) Hex:EtOAc)] to give the title compound

Reference： [1]Carreiro, Elisabete P.; Louro, Patrícia; Adriano, Gizé; Guedes, Romina A.; Vannuchi, Nicholas; Costa, Ana R.; Antunes, Célia M.M.; Guedes, Rita C.; Burke [Bioorganic Chemistry, 2014, vol. 54, p. 81 - 88]

38
[ 122929-12-8 ]
[ 101385-90-4 ]
[ 101385-90-4 ]
[ 124445-27-8 ]

Yield	Reaction Conditions	Operation in experiment
	With Rhizomucor miehei lipase Palatase; In aq. phosphate buffer; tert-butyl methyl ether; at 20℃; for 6h;pH 7.0;Enzymatic reaction;	General procedure: The reactions were conducted at room temperature in suitable vessels, using a vortex mixer. In a typical small scale experiment, to a solution of racemic ester (10 mg) in potassium phosphate buffer (50 mM, pH 7) or in a potassium phosphate buffer/organic solvent mixture (1 mL), native (2 mg) or immobilized (200 mg) enzymes were added. The reactions were monitored by HPLC by taking samples at different intervals of time. The reaction mixture was extracted with dichloromethane (2 x 0.5 mL). The organic layer was dried over sodium sulfate, concentrated at reduced pressure and analysed by HPLC as described in Section 4.2. Data on reaction times, conversion and enantiomeric excess of the substrates and the products are presented in Tables 1-4.

Reference： [1]Tetrahedron Asymmetry,2015,vol. 26,p. 638 - 643

39
[ 122929-12-8 ]
[ 101385-90-4 ]
[ 101385-90-4 ]
[ 116143-02-3 ]
[ 124445-27-8 ]

Yield	Reaction Conditions	Operation in experiment
	With Aspergillus niger lipase AS; In aq. phosphate buffer; tert-butyl methyl ether; at 20℃; for 23h;pH 7.0;Enzymatic reaction;	General procedure: The reactions were conducted at room temperature in suitable vessels, using a vortex mixer. In a typical small scale experiment, to a solution of racemic ester (10 mg) in potassium phosphate buffer (50 mM, pH 7) or in a potassium phosphate buffer/organic solvent mixture (1 mL), native (2 mg) or immobilized (200 mg) enzymes were added. The reactions were monitored by HPLC by taking samples at different intervals of time. The reaction mixture was extracted with dichloromethane (2 x 0.5 mL). The organic layer was dried over sodium sulfate, concentrated at reduced pressure and analysed by HPLC as described in Section 4.2. Data on reaction times, conversion and enantiomeric excess of the substrates and the products are presented in Tables 1-4.
	With Candida antarctica A lipase CAL-A; In aq. phosphate buffer; tert-butyl methyl ether; at 20℃; for 5h;pH 7.0;Enzymatic reaction;	General procedure: The reactions were conducted at room temperature in suitable vessels, using a vortex mixer. In a typical small scale experiment, to a solution of racemic ester (10 mg) in potassium phosphate buffer (50 mM, pH 7) or in a potassium phosphate buffer/organic solvent mixture (1 mL), native (2 mg) or immobilized (200 mg) enzymes were added. The reactions were monitored by HPLC by taking samples at different intervals of time. The reaction mixture was extracted with dichloromethane (2 x 0.5 mL). The organic layer was dried over sodium sulfate, concentrated at reduced pressure and analysed by HPLC as described in Section 4.2. Data on reaction times, conversion and enantiomeric excess of the substrates and the products are presented in Tables 1-4.

Reference： [1]Tetrahedron Asymmetry,2015,vol. 26,p. 638 - 643
[2]Tetrahedron Asymmetry,2015,vol. 26,p. 638 - 643

40
[ 122929-12-8 ]
[ 101385-90-4 ]
[ 101385-90-4 ]
[ 116143-02-3 ]

Yield	Reaction Conditions	Operation in experiment
	With Bacillus licheniformis immobilized protease Alcalase-IM; In aq. phosphate buffer; tert-butyl methyl ether; at 20℃; for 7h;pH 7.0;Enzymatic reaction;	General procedure: The reactions were conducted at room temperature in suitable vessels, using a vortex mixer. In a typical small scale experiment, to a solution of racemic ester (10 mg) in potassium phosphate buffer (50 mM, pH 7) or in a potassium phosphate buffer/organic solvent mixture (1 mL), native (2 mg) or immobilized (200 mg) enzymes were added. The reactions were monitored by HPLC by taking samples at different intervals of time. The reaction mixture was extracted with dichloromethane (2 x 0.5 mL). The organic layer was dried over sodium sulfate, concentrated at reduced pressure and analysed by HPLC as described in Section 4.2. Data on reaction times, conversion and enantiomeric excess of the substrates and the products are presented in Tables 1-4.

Reference： [1]Tetrahedron Asymmetry,2015,vol. 26,p. 638 - 643

41
[ 122929-12-8 ]
[ 101930-07-8 ]
[ 116143-02-3 ]
[ 124445-27-8 ]

Yield	Reaction Conditions	Operation in experiment
1: > 99.5 % ee 2: 84 % ee	With Pseudomonas fluorescens immobilized lipase AK-IM In aq. phosphate buffer; tert-butyl methyl ether at 20℃; for 7h; Enzymatic reaction; enantioselective reaction;	5.1 Analytical scale enzymatic hydrolysis of rac-3-5 General procedure: The reactions were conducted at room temperature in suitable vessels, using a vortex mixer. In a typical small scale experiment, to a solution of racemic ester (10 mg) in potassium phosphate buffer (50 mM, pH 7) or in a potassium phosphate buffer/organic solvent mixture (1 mL), native (2 mg) or immobilized (200 mg) enzymes were added. The reactions were monitored by HPLC by taking samples at different intervals of time. The reaction mixture was extracted with dichloromethane (2 x 0.5 mL). The organic layer was dried over sodium sulfate, concentrated at reduced pressure and analysed by HPLC as described in Section 4.2. Data on reaction times, conversion and enantiomeric excess of the substrates and the products are presented in Tables 1-4.

Reference： [1]Tofani, Giorgio; Petri, Antonella; Piccolo, Oreste [Tetrahedron Asymmetry, 2015, vol. 26, # 12-13, p. 638 - 643]

42
[ 775-16-6 ]
[ 101385-90-4 ]

Yield	Reaction Conditions	Operation in experiment
90%	With recombinant Chryseobacterium sp. CA 49 ketoreductase; nicotinamide adenine dinucleotide; In aq. phosphate buffer; isopropyl alcohol; at 40℃; for 24h;pH 7.0;Enzymatic reaction;Catalytic behavior;	General procedure: The reaction mixture containing 200 mM substrate, 1mM NAD+, 5% (v/v) 2-propanol and 10mg crude enzyme READH in 1mL potassium phosphate buffer (100mM, pH 7.0) was incubated at 50 C. For ChKRED20, 40% (v/v) 2-propanol and a reaction temperature of 40 C were applied instead. The reaction was monitored by TLC, and terminated by extracting with methyl tert-butyl ether (1 mL). The organic extract was dried over anhydrous sodium sulfate and concentrated. The samples were subjected to chiral HPLC to determine the conversion and enantiomeric excess. The products were purified by silica gel column chromatography, and identified by NMR analysis, optical rotation measurements and mass spectrometry.

Reference： [1]Process Biochemistry,2017,vol. 56,p. 90 - 97

43
[ 101385-90-4 ]
[ 775-16-6 ]

Reference： [1]Organic Process Research and Development,2017,vol. 21,p. 1419 - 1422

Same Skeleton Products

Related Products

Historical Records

Related Functional Groups of
[ 101930-07-8 ]

Aryls

[ 775-15-5 ]

1-Benzyl-3-pyrrolidinol

Similarity: 1.00

[ 101385-90-4 ]

(S)-1-Benzylpyrrolidin-3-ol

Similarity: 1.00

[ 163439-82-5 ]

(3R,4R)-1-Benzylpyrrolidine-3,4-diol

Similarity: 0.97

[ 90365-74-5 ]

(3S,4S)-1-Benzyl-3,4-pyrrolidindiol

Similarity: 0.97

[ 1346224-27-8 ]

(3R,4S)-1-Benzylpyrrolidine-3,4-diol

Similarity: 0.97

Alcohols

[ 775-15-5 ]

1-Benzyl-3-pyrrolidinol

Similarity: 1.00

[ 101385-90-4 ]

(S)-1-Benzylpyrrolidin-3-ol

Similarity: 1.00

[ 163439-82-5 ]

(3R,4R)-1-Benzylpyrrolidine-3,4-diol

Similarity: 0.97

[ 90365-74-5 ]

(3S,4S)-1-Benzyl-3,4-pyrrolidindiol

Similarity: 0.97

[ 1346224-27-8 ]

(3R,4S)-1-Benzylpyrrolidine-3,4-diol

Similarity: 0.97

Related Parent Nucleus of
[ 101930-07-8 ]

Pyrrolidines

[ 775-15-5 ]

1-Benzyl-3-pyrrolidinol

Similarity: 1.00

[ 101385-90-4 ]

(S)-1-Benzylpyrrolidin-3-ol

Similarity: 1.00

[ 163439-82-5 ]

(3R,4R)-1-Benzylpyrrolidine-3,4-diol

Similarity: 0.97

[ 90365-74-5 ]

(3S,4S)-1-Benzyl-3,4-pyrrolidindiol

Similarity: 0.97

[ 1346224-27-8 ]

(3R,4S)-1-Benzylpyrrolidine-3,4-diol

Similarity: 0.97

Purity	Size	Price	VIP Price	USA Stock *0-1 Day	Global Stock *5-7 Days	Quantity
{[ item.p_purity ]}	{[ item.pr_size ]}	{[ getRatePrice(item.pr_usd, 1,1) ]} {[ getRatePrice(item.pr_usd,item.pr_rate,item.mem_rate) ]}	{[ getRatePrice(item.pr_usd, 1,1) ]}	Inquiry {[ getRatePrice(item.pr_usd,item.pr_rate,item.mem_rate) ]} {[ getRatePrice(item.pr_usd,1,item.mem_rate) ]}	{[ item.pr_usastock ]}	Inquiry -	{[ item.pr_chinastock ]}	Inquiry -

Precautionary Statements-General
Code	Phrase
P101	If medical advice is needed,have product container or label at hand.
P102	Keep out of reach of children.
P103	Read label before use
Prevention
Code	Phrase
P201	Obtain special instructions before use.
P202	Do not handle until all safety precautions have been read and understood.
P210	Keep away from heat/sparks/open flames/hot surfaces. - No smoking.
P211	Do not spray on an open flame or other ignition source.
P220	Keep/Store away from clothing/combustible materials.
P221	Take any precaution to avoid mixing with combustibles
P222	Do not allow contact with air.
P223	Keep away from any possible contact with water, because of violent reaction and possible flash fire.
P230	Keep wetted
P231	Handle under inert gas.
P232	Protect from moisture.
P233	Keep container tightly closed.
P234	Keep only in original container.
P235	Keep cool
P240	Ground/bond container and receiving equipment.
P241	Use explosion-proof electrical/ventilating/lighting/equipment.
P242	Use only non-sparking tools.
P243	Take precautionary measures against static discharge.
P244	Keep reduction valves free from grease and oil.
P250	Do not subject to grinding/shock/friction.
P251	Pressurized container: Do not pierce or burn, even after use.
P260	Do not breathe dust/fume/gas/mist/vapours/spray.
P261	Avoid breathing dust/fume/gas/mist/vapours/spray.
P262	Do not get in eyes, on skin, or on clothing.
P263	Avoid contact during pregnancy/while nursing.
P264	Wash hands thoroughly after handling.
P265	Wash skin thouroughly after handling.
P270	Do not eat, drink or smoke when using this product.
P271	Use only outdoors or in a well-ventilated area.
P272	Contaminated work clothing should not be allowed out of the workplace.
P273	Avoid release to the environment.
P280	Wear protective gloves/protective clothing/eye protection/face protection.
P281	Use personal protective equipment as required.
P282	Wear cold insulating gloves/face shield/eye protection.
P283	Wear fire/flame resistant/retardant clothing.
P284	Wear respiratory protection.
P285	In case of inadequate ventilation wear respiratory protection.
P231 + P232	Handle under inert gas. Protect from moisture.
P235 + P410	Keep cool. Protect from sunlight.
Response
Code	Phrase
P301	IF SWALLOWED:
P304	IF INHALED:
P305	IF IN EYES:
P306	IF ON CLOTHING:
P307	IF exposed:
P308	IF exposed or concerned:
P309	IF exposed or if you feel unwell:
P310	Immediately call a POISON CENTER or doctor/physician.
P311	Call a POISON CENTER or doctor/physician.
P312	Call a POISON CENTER or doctor/physician if you feel unwell.
P313	Get medical advice/attention.
P314	Get medical advice/attention if you feel unwell.
P315	Get immediate medical advice/attention.
P320
P302 + P352	IF ON SKIN: wash with plenty of soap and water.
P321
P322
P330	Rinse mouth.
P331	Do NOT induce vomiting.
P332	IF SKIN irritation occurs:
P333	If skin irritation or rash occurs:
P334	Immerse in cool water/wrap n wet bandages.
P335	Brush off loose particles from skin.
P336	Thaw frosted parts with lukewarm water. Do not rub affected area.
P337	If eye irritation persists:
P338	Remove contact lenses, if present and easy to do. Continue rinsing.
P340	Remove victim to fresh air and keep at rest in a position comfortable for breathing.
P341	If breathing is difficult, remove victim to fresh air and keep at rest in a position comfortable for breathing.
P342	If experiencing respiratory symptoms:
P350	Gently wash with plenty of soap and water.
P351	Rinse cautiously with water for several minutes.
P352	Wash with plenty of soap and water.
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. 101930-07-8 ] {[proInfo.proName]}

Quality Control of [ 101930-07-8 ]

Related Doc. of [ 101930-07-8 ]

Product Details of [ 101930-07-8 ]

Calculated chemistry of [ 101930-07-8 ]

Physicochemical Properties

Pharmacokinetics

Lipophilicity

Druglikeness

Water Solubility

Medicinal Chemistry

Safety of [ 101930-07-8 ]

Application In Synthesis of [ 101930-07-8 ]

[ 101930-07-8 ] Synthesis Path-Downstream 1~43

Related Functional Groups of [ 101930-07-8 ]

Aryls

Alcohols

Related Parent Nucleus of [ 101930-07-8 ]

Pyrrolidines

Precautionary Statements-General

Prevention

Response

Storage

Disposal

Physical hazards

Health hazards

Environmental hazards

Inquiry

Related Functional Groups of
[ 101930-07-8 ]

Related Parent Nucleus of
[ 101930-07-8 ]