[ CAS No. 19740-72-8 ] {[proInfo.proName]}

Name: 19740-72-8|Diisopropyl hydrazine-1,2-dicarboxylate|97%
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SKU: A203934
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Quality Control of [ 19740-72-8 ]

COA NMR CNMR HPLC LC-MS

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SDS Specification

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Product Details of [ 19740-72-8 ]

CAS No. :	19740-72-8	MDL No. :	MFCD19443326
Formula :	C₈H₁₆N₂O₄	Boiling Point :	-
Linear Structure Formula :	-	InChI Key :	FBZULTVJWVCJQV-UHFFFAOYSA-N
M.W :	204.22	Pubchem ID :	88220
Synonyms :

Calculated chemistry of [ 19740-72-8 ]

Physicochemical Properties

Num. heavy atoms :	14
Num. arom. heavy atoms :	0
Fraction Csp3 :	0.75
Num. rotatable bonds :	7
Num. H-bond acceptors :	4.0
Num. H-bond donors :	2.0
Molar Refractivity :	49.52
TPSA :	76.66 Å²

Pharmacokinetics

GI absorption :	High
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) :	-6.51 cm/s

Lipophilicity

Log Po/w (iLOGP) :	2.02
Log Po/w (XLOGP3) :	1.46
Log Po/w (WLOGP) :	1.17
Log Po/w (MLOGP) :	0.91
Log Po/w (SILICOS-IT) :	-0.56
Consensus Log Po/w :	1.0

Druglikeness

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

Water Solubility

Log S (ESOL) :	-1.56
Solubility :	5.57 mg/ml ; 0.0273 mol/l
Class :	Very soluble
Log S (Ali) :	-2.68
Solubility :	0.431 mg/ml ; 0.00211 mol/l
Class :	Soluble
Log S (SILICOS-IT) :	-1.01
Solubility :	19.8 mg/ml ; 0.0968 mol/l
Class :	Soluble

Medicinal Chemistry

PAINS :	0.0 alert
Brenk :	1.0 alert
Leadlikeness :	1.0
Synthetic accessibility :	2.68

Safety of [ 19740-72-8 ]

Signal Word:	Danger	Class:	6.1,4.1
Precautionary Statements:	P210-P240-P241-P264-P270-P280-P310-P330-P370+P378-P405-P501	UN#:	2930
Hazard Statements:	H301-H228	Packing Group:	Ⅱ
GHS Pictogram:

Application In Synthesis of [ 19740-72-8 ]

* 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.

Upstream synthesis route of [ 19740-72-8 ]
Downstream synthetic route of [ 19740-72-8 ]

[ 19740-72-8 ] Synthesis Path-Upstream 1~4

1
[ 19740-72-8 ]
[ 2446-83-5 ]

Yield	Reaction Conditions	Operation in experiment
77.8%	With pyridine; N-Bromosuccinimide In toluene at 20℃; for 2 h;	To a 30 ml flask, hydrazine hydrate (200 mg, 4.0 mmol),Tetrahydrofuran (10 ml)And sodium carbonate (551 mg, 5.2 mmol) were added, and under ice cooling,Chlorocarbonic acid isopropyl ester (980 mg, 8.0 mmol) was added dropwise, followed by reaction for 1 hour.After completion of the reaction, the solid was removed by filtration, and the obtained filtrate was concentrated to about 90 vol percent of 1,2-hydrazinedicarboxylic acid diisopropyl ester to give tetrahydrofuranToluene (10 ml) was added, and the remaining tetrahydrofuran was removed by concentration to give 1, A toluene solution of 2-hydrazinedicarboxylic acid diisopropyl ester was obtained.Then, pyridine (316.4 mg, 4.0 mmol) was added to a toluene solution of 1,2-hydrazinedicarboxylic acid diisopropyl ester,, And toluene (10 ml) were added, and N-bromosuccinimide (711.9 mg, 4.0 mmol) was slowly added at 20 ° C. and reacted for 2 hours.After completion of the reaction, the solution was washed with water (3 mL × 2 times), dehumidified with anhydrous magnesium sulfate, and concentrated to dryness. The residue was distilled to obtain diisopropyl azodicarboxylate as a clear solution(628.5 mg, yield 77.8percent)

Reference： [1] Organic Letters, 2016, vol. 18, # 24, p. 6300 - 6303
[2] Patent: JP5920622, 2016, B2, . Location in patent: Paragraph 0029-0031
[3] Journal of Organic Chemistry USSR (English Translation), 1971, vol. 7, # 11, p. 2361 - 2364[4] Zhurnal Organicheskoi Khimii, 1971, vol. 7, # 11, p. 2271 - 2274
[5] Organic and Biomolecular Chemistry, 2017, vol. 15, # 9, p. 1970 - 1975

2
[ 95-57-8 ]
[ 2446-83-5 ]
[ 19740-72-8 ]
[ 3964-56-5 ]

Reference： [1] Tetrahedron Letters, 2008, vol. 49, # 11, p. 1729 - 1733

3
[ 87-65-0 ]
[ 2446-83-5 ]
[ 19740-72-8 ]
[ 3217-15-0 ]

Reference： [1] Tetrahedron Letters, 2008, vol. 49, # 11, p. 1729 - 1733

4
[ 1570-64-5 ]
[ 2446-83-5 ]
[ 19740-72-8 ]
[ 54852-68-5 ]

Reference： [1] Tetrahedron Letters, 2008, vol. 49, # 11, p. 1729 - 1733

[ 19740-72-8 ] Synthesis Path-Downstream 1~64

1
[ 19740-72-8 ]
[ 2446-83-5 ]

Yield	Reaction Conditions	Operation in experiment
77.8%	With pyridine; N-Bromosuccinimide; In toluene; at 20℃; for 2h;	To a 30 ml flask, hydrazine hydrate (200 mg, 4.0 mmol),Tetrahydrofuran (10 ml)And sodium carbonate (551 mg, 5.2 mmol) were added, and under ice cooling,Chlorocarbonic acid isopropyl ester (980 mg, 8.0 mmol) was added dropwise, followed by reaction for 1 hour.After completion of the reaction, the solid was removed by filtration, and the obtained filtrate was concentrated to about 90 vol% of 1,2-hydrazinedicarboxylic acid diisopropyl ester to give tetrahydrofuranToluene (10 ml) was added, and the remaining tetrahydrofuran was removed by concentration to give 1, A toluene solution of 2-hydrazinedicarboxylic acid diisopropyl ester was obtained.Then, pyridine (316.4 mg, 4.0 mmol) was added to a toluene solution of 1,2-hydrazinedicarboxylic acid diisopropyl ester,, And toluene (10 ml) were added, and N-bromosuccinimide (711.9 mg, 4.0 mmol) was slowly added at 20 C. and reacted for 2 hours.After completion of the reaction, the solution was washed with water (3 mL × 2 times), dehumidified with anhydrous magnesium sulfate, and concentrated to dryness. The residue was distilled to obtain diisopropyl azodicarboxylate as a clear solution(628.5 mg, yield 77.8%)

Reference： [1]Organic Letters,2016,vol. 18,p. 6300 - 6303
[2]Patent: JP5920622,2016,B2 .Location in patent: Paragraph 0029-0031
[3]Journal of Organic Chemistry USSR (English Translation),1971,vol. 7,p. 2361 - 2364
Zhurnal Organicheskoi Khimii,1971,vol. 7,p. 2271 - 2274
[4]Organic and Biomolecular Chemistry,2017,vol. 15,p. 1970 - 1975

2
[ 19740-72-8 ]
[ 72195-20-1 ]

Yield	Reaction Conditions	Operation in experiment
	With sulfur dichloride; triethylamine In diethyl ether

Reference： [1]Weinstein,B. et al. [Journal of Heterocyclic Chemistry, 1979, vol. 16, p. 751 - 752]

3
[ 19740-72-8 ]
[ 72195-18-7 ]

Yield	Reaction Conditions	Operation in experiment
	With thionyl chloride; triethylamine In diethyl ether

Reference： [1]Weinstein,B. et al. [Journal of Heterocyclic Chemistry, 1979, vol. 16, p. 751 - 752]

4
[ 108-23-6 ]
[ 19740-72-8 ]

Yield	Reaction Conditions	Operation in experiment
33%	With hydrazine In ethanol; water at 10 - 20℃; for 0.5h;
	With hydrazine hydrate In water
	With sodium carbonate; hydrazine hydrate In tetrahydrofuran for 1h; Cooling with ice;	3 To a 30 ml flask, hydrazine hydrate (200 mg, 4.0 mmol),Tetrahydrofuran (10 ml)And sodium carbonate (551 mg, 5.2 mmol) were added, and under ice cooling,Chlorocarbonic acid isopropyl ester (980 mg, 8.0 mmol) was added dropwise, followed by reaction for 1 hour.After completion of the reaction, the solid was removed by filtration, and the obtained filtrate was concentrated to about 90 vol% of 1,2-hydrazinedicarboxylic acid diisopropyl ester to give tetrahydrofuranToluene (10 ml) was added, and the remaining tetrahydrofuran was removed by concentration to give 1, A toluene solution of 2-hydrazinedicarboxylic acid diisopropyl ester was obtained.Then, pyridine (316.4 mg, 4.0 mmol) and toluene (10 ml) were added to a toluene solution of 1,2-hydrazinedicarboxylic acid diisopropyl ester, and N-bromosuccinimide (711.9 mg, 4.0 mmol ) Was slowly added and reacted for 2 hours.After completion of the reaction, the solution was washed with water (3 mL × 2 times), dehumidified with anhydrous magnesium sulfate, and concentrated to dryness. The residue was distilled to obtain diisopropyl azodicarboxylate as a clear solution(628.5 mg, yield 77.8%)

Reference： [1]März; Chudoba; Kohout; Cibulka [Organic and Biomolecular Chemistry, 2017, vol. 15, # 9, p. 1970 - 1975]
[2]Rodkin,S.A. et al. [Journal of Organic Chemistry USSR (English Translation), 1971, vol. 7, # 11, p. 2361 - 2364][Zhurnal Organicheskoi Khimii, 1971, vol. 7, # 11, p. 2271 - 2274]
[3]Current Patent Assignee: TOYOBO CO LTD - JP5920622, 2016, B2 Location in patent: Paragraph 0029; 0031

5
[ 63148-50-5 ]
[ 19740-72-8 ]
[ 78076-78-5 ]

Yield	Reaction Conditions	Operation in experiment
	With triethylamine In benzene for 3h; Ambient temperature;

Reference： [1]Tautz, Helmut; Schmidpeter, Alfred [Chemische Berichte, 1981, vol. 114, # 2, p. 825 - 828]

6
[ 625-84-3 ]
[ 2446-83-5 ]
[ 19740-72-8 ]

Reference： [1]Tetrahedron Letters,1980,vol. 21,p. 3673 - 3676

7
[ 197-69-3 ]
[ 2446-83-5 ]
[ 19740-72-8 ]
[ 81376-61-6 ]

Reference： [1]Synthesis,1982,p. 229 - 231

8
[ 19740-72-8 ]
1-Hydroxy-1,2,3,4,7,8,13,13b-octahydro<1,2>-oxazepino<2',3':1,2>pyrido<3,4-b>indole [ No CAS ]
(S)-3-Isopropoxy-8,11,12,13,13a,13b-hexahydro-9H-10-oxa-1,2,3a,9a-tetraaza-benzo[6,7]cyclohepta[1,2,3-jk]fluorene-1-carboxylic acid isopropyl ester [ No CAS ]
(R)-3-Isopropoxy-8,11,12,13,13a,13b-hexahydro-9H-10-oxa-1,2,3a,9a-tetraaza-benzo[6,7]cyclohepta[1,2,3-jk]fluorene-1-carboxylic acid isopropyl ester [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
	With phthalimide; triphenylphosphine In tetrahydrofuran for 1.5h; Title compound not separated from byproducts;

Reference： [1]Maarseveen, Jan H. van; Oberye, Elna H. H.; Bolster, Marjon B.; Scheeren, Hans W.; Kruse, Chris G. [Recueil des Travaux Chimiques des Pays-Bas, 1995, vol. 114, # 1, p. 27 - 34]

9
[ 2446-83-5 ]
[ 19740-72-8 ]
N-(chloroacetyl)-N,N'-bis(isopropylcarboxy)hydrazine [ No CAS ]
N,N'-bis(chloroacetyl)-N,N'-bis(isopropylcarboxy)hydrazine [ No CAS ]

Reference： [1]Journal of Organic Chemistry,1996,vol. 61,p. 2967 - 2971

10
[ 2446-83-5 ]
[ 64-19-7 ]
[ 19740-72-8 ]
N-acetyl-N,N'-bis(isopropylcarboxy)hydrazine [ No CAS ]
N,N'-diacetyl-N,N'-bis(isopropylcarboxy)hydrazine [ No CAS ]

Reference： [1]Journal of Organic Chemistry,1996,vol. 61,p. 2967 - 2971

11
[ 2446-83-5 ]
[ 79-11-8 ]
[ 19740-72-8 ]
N-(chloroacetyl)-N,N'-bis(isopropylcarboxy)hydrazine [ No CAS ]
N,N'-bis(chloroacetyl)-N,N'-bis(isopropylcarboxy)hydrazine [ No CAS ]

Reference： [1]Journal of Organic Chemistry,1996,vol. 61,p. 2967 - 2971

12
[ 2446-83-5 ]
[ 65-85-0 ]
[ 19740-72-8 ]
[ 93-97-0 ]
1-benzoyl-1,2-hydrazinedicarboxylic acid 1,2-diisopropyl ester [ No CAS ]
N,N'-dibenzoyl-N,N'-bis(isopropyloxycarbonyl)hydrazine [ No CAS ]

Reference： [1]Journal of Organic Chemistry,1996,vol. 61,p. 2967 - 2971
[2]Journal of Organic Chemistry,1996,vol. 61,p. 2967 - 2971

13
[ 2446-83-5 ]
[ 50-89-5 ]
[ 19740-72-8 ]
[ 15981-92-7 ]
3'-deoxy-3'β-(N,N-diisopropyloxycarbonylhydrazino)thymidine [ No CAS ]
[ 175545-73-0 ]

Reference： [1]Nucleosides and Nucleotides,1996,vol. 15,p. 899 - 906

14
[ 2446-83-5 ]
[ 62-23-7 ]
[ 19740-72-8 ]
N-(4-nitrobenzoyl)-N,N'-bis(isopropylcarboxy)hydrazine [ No CAS ]
N,N'-bis(4-nitrobenzoyl)-N,N'-bis(isopropylcarboxy)hydrazine [ No CAS ]

Reference： [1]Journal of Organic Chemistry,1996,vol. 61,p. 2967 - 2971

15
[ 19740-72-8 ]
[ 603-35-0 ]
ytriphenylphosphine oxide - diisopropyl hydrazinedicarboxylate [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
	With hydrogen azide; 3-methylpentane-1,5-diol In tetrahydrofuran; benzene

Reference： [1]Heroux; Brisse [Acta Crystallographica, Section C: Crystal Structure Communications, 1997, vol. 53, # 9, p. 1318 - 1320]

16
[ 2446-83-5 ]
[ 603-35-0 ]
[ 65-85-0 ]
[ 19740-72-8 ]
[ 93-97-0 ]
[ 791-28-6 ]

Yield	Reaction Conditions	Operation in experiment
1: 14 % Spectr. 2: /PMDLI319-1150/\76 % Spectr.	In tetrahydrofuran at 24℃; for 2h; various reagent ratios;

Reference： [1]Harvey, Peta J.; Von Itzstein, Mark; Jenkins, Ian D. [Tetrahedron, 1997, vol. 53, # 11, p. 3933 - 3942]

Yield	Reaction Conditions	Operation in experiment
	Rk. mit HNO3;

19
[ 2446-83-5 ]
[ 19740-72-8 ]

Reference： [1]Angewandte Chemie - International Edition,2006,vol. 45,p. 2305 - 2308

20
[ 2446-83-5 ]
[ 529-33-9 ]
[ 5451-40-1 ]
2,6-dichloro-9-(1,2,3,4-tetrahydronaphthalen-1-yl)-9H-purine [ No CAS ]
2,6-dichloro-7-(1,2,3,4-tetrahydronaphthalen-1-yl)-7H-purine [ No CAS ]
[ 19740-72-8 ]

Reference： [1]Journal of Organic Chemistry,2007,vol. 72,p. 5012 - 5015

21
[ 2446-83-5 ]
[ 6351-10-6 ]
[ 87-42-3 ]
6-chloro-9-(2,3-dihydro-1H-inden-1-yl)-9H-purine [ No CAS ]
[ 19740-72-8 ]

Reference： [1]Journal of Organic Chemistry,2007,vol. 72,p. 5012 - 5015

22
[ 2446-83-5 ]
[ 6351-10-6 ]
[ 5451-40-1 ]
2,6-dichloro-9-(2,3-dihydro-1H-inden-1-yl)-9H-purine [ No CAS ]
2,6-dichloro-7-(2,3-dihydro-1H-inden-1-yl)-7H-purine [ No CAS ]
[ 19740-72-8 ]

Reference： [1]Journal of Organic Chemistry,2007,vol. 72,p. 5012 - 5015

23
[ 108-43-0 ]
[ 2446-83-5 ]
[ 74844-91-0 ]
[ 686766-55-2 ]
[ 19740-72-8 ]

Yield	Reaction Conditions	Operation in experiment
	With triphenylphosphine; In tetrahydrofuran; at 0 - 20℃; for 72h;	To a stirred solution of (2S, 4R)-4-hydroxy-pyrrolidine-1, 2-dicarboxylic acid 1-tert- butyl ester 2-methyl ester (CAS Reg. No. 74844-91-0) (0.3g, 1. 22mmol), 3-chlorophenol (0. 189g, 1. 47MMOL) and triphenylphosphine (0. 385G, 1. 47MMOL) in THF (2ml) cooled at 0C under N2 was added dropwise the diisopropylazodicarboxylate (0. 29ml, 1. 47MMOL). The mixture was stirred for 3 days at room temperature. The solvent was removed in vacuo and the product was purified by chromatography on silica gel using ether/n- pentane: 40/60 as eluent to afford 0. 27G (62%) of a mixture of the title compound and reduced diisopropyl AZODICARBOXYLATE (1/1) as an oil. 'H NMR (400MHZ, CDC13) : 8 = 1.46, 1.49 (2 x s, 9H), 2.47 (2H, m), 3.71 (5H, m), 4.42 (1H, m), 4.42, 4.54 (1H, 2 x m), 4.87 (1H, m), 6.68 (1H, m), 6.79 (1H, s), 6.92 (1H, m), 7.18 (1H, m). LRMS (ELECTROSPRAY) : m/z 378 (MNa+).

Reference： [1]Patent: WO2004/39367,2004,A1 .Location in patent: Page/Page column 66-67

24
[ 4984-22-9 ]
[ 54915-31-0 ]
[ 851885-42-2 ]
[ 19740-72-8 ]

Yield	Reaction Conditions	Operation in experiment
	With PS-triphenylphosphine; di-isopropyl azodicarboxylate In tetrahydrofuran for 0.5h;	Methyl 3-r (lS)-1-methyl-2-methoxv-ethoxv-5-benzvloxe-benzoate; To a solution of methyl 3-hydroxy-5- [ (phenylmethyl) oxy] benzoate (77.4 mmol) in THF was added polymer-supported triphenylphosphine (51.7g of 3 mmol/g loading, 155mmol) and (R)- (-)-1-methoxy-2-propanol (102 mmol). The stirred solution was blanketed with argon and cooled in an ice bath; a solution of diisopropyl azodicarboxylate (116 mmol) was added dropwise from a syringe over 10 minutes. After addition the solution was stirred for 20 minutes and then filtered, washing the residue with THF (500 mL); the filtrate and washings were combined and evaporated to give crude desired compound which was used in the next step without further purification. 'H NMR 8 (d6-DMSO) : 3.26 (s, 3H), 3.44 (m, 2H), 3.82 (s, 3H), 4.63 (m, 1H), 5.14 (s, 2H), 6.85 (s, 1H), 7.05 (s, 1H), 7.11 (s, 1H), 7.30-7. 47 (m, 5H) ; the spectrum also contained signals consistent with a small amount of bis (1-methylethyl) hydrazine-1,2-dicarboxylate.

Reference： [1]Current Patent Assignee: ASTRAZENECA PLC - WO2005/54200, 2005, A1 Location in patent: Page/Page column 26-27

25
[ 4984-22-9 ]
[ 2446-83-5 ]
[ 54915-31-0 ]
[ 851885-42-2 ]
[ 19740-72-8 ]

Yield	Reaction Conditions	Operation in experiment
	With triphenylphosphine on polystyrene; In tetrahydrofuran; at 0℃; for 0.5h;	Methyl 3-[(1S)-2-methoxy-(1-methylethyl)oxy]-5-[phenylmethyl]oxy}benzoic; To a solution of methyl 3-hydroxy-5-[phenylmethyl] oxy} benzoate (77.4 mmol) in THF was added polymer-supported triphenylphosphine (51.7g of 3 mmol/g loading, 155 mmol) and (R)- (-)-l-methoxy-2-propanol (102 mmol). The stirred solution was blanketed with argon and cooled in an ice bath. A solution of DIAD (116 mmol) was added dropwise by syringe over 10 minutes. The solution was stirred for 20 minutes and filtered, washing the residue with THF (500 mL). The filtrate and washings were combined, and evaporated to give the desired compound which was used without further purification. 'H NMR 6 (d6-DMSO) : 3.26 (s, 3H), 3.44 (m, 2H), 3.82 (s, 3H), 4.63 (m, 1H), 5.14 (s, 2H), 6.85 (s, 1H), 7.05 (s, 1H), 7.11 (s, 1H), 7.30-7. 47 (m, 5H) The 1H NMR spectrum also contained signals consistent with a small amount of bis (l- methylethyl) hydrazine-1, 2-dicarboxylate.

Reference： [1]Patent: WO2005/80359,2005,A1 .Location in patent: Page/Page column 73

26
[ 170100-49-9 ]
[ 998-40-3 ]
[ 2446-83-5 ]
[ 64-19-7 ]
[ 618107-23-6 ]
[ 814-29-9 ]
[ 19740-72-8 ]

Yield	Reaction Conditions	Operation in experiment
	In n-heptane; at -5 - 25℃; for 2.75h;	Preparation of S- (+)-2-hydroxy-4- [3-hydroxy- 3- (5, 6, 7, 8-tetrahydro-5, 5, 8, 8-tetramethyl-2-naphthyl)- 1-propynyl]benzoic acid from 1-(5, 6, 7, 8-tetrahydro- 5, 5, 8, 8-tetramethyl-2-naphthyl) prop-2-yn-1-ol The compound 1- (5, 6,7, 8-tetrahydro-5, 5,8, 8- tetramethyl-2-naphthyl) prop-2-yn-1-ol (31.0 kg) is placed in contact with lipase PS 30 Amano (6.2 kg) and vinyl acetate (11.0 kg) at a-temperature below 40C, in the presence of heptane (47-litres). The mixture is heated at a temperature of about 36 to 40C for 33 hours with mechanical stirring. The mixture is then cooled to a temperature of about 25/30C. The enzyme in suspension is then filtered from the reaction mixture containing the acetate of desired R configuration and the alcohol of S configuration. The mixture is heated again to 40/50C so as to evaporate to constant volume, by adding heptane, the majority of the solvents and reagents. A mixture of 33 kg of alcohol of S configuration and of acetate of R. configuration dissolved in the heptane is thus obtained. 10 litres of heptane cooled to 0/-5C are added to the solution of S alcohol and R acetate obtained above, and 14.3 kg of tri-n-butylphosphine (TBP) are added at a temperature below 25C, in the presence of 4.22 kg of 99% acetic acid at a temperature below 7C. The mixture is cooled to 0/5C, followed by addition of 14.5 kg of <strong>[2446-83-5]diisopropyl azodicarboxylate</strong> (DIAD) at a temperature below 5C. The mixture is then heated-to a temperature of about 20C and maintained at this temperature for 2 hours 45 minutes. The phosphine oxide and the DIAD derivative obtained along with the acetate of desired configuration are removed by liquid-liquid extraction (2 extractions with 5 volumes of methanol/water mixture (85: 15), then 2 back-extractions with 5 volumes of heptane, and then 1'extraction with 5 volumes of methanol/water (85: 15) ). The transesterification of. the R acetate is performed in the presence of sodium carbonate (27.1 kg) and methanol (155 litres), by heating the mixture at 40C for 7 hours 15 minutes. After adding a heptane/water mixture (50: 50), the reaction mixture is again heated to 60/65C to remove. the methanol by distillation. After separation of the organic and aqueous phases,. the crystallization is performed by cooling the organic layer obtained to the point of crystallization and then maintaining it at a temperature below-5C for 30 minutes. After filtration followed by drying for about 11 hours at a maximum temperature of 30C, the R (-) enantiomer of 1- (5, 6,7, 8-tetrahydro-5, 5,8, 8- tetramethyl-2-naphthyl) prop-2-yn-1-ol (18.4 kg) is obtained. The overall chemical yield for the production of this alcohol of R configuration from the racemic mixture is 60% and the chiral purity of the compound is 99%.

Reference： [1]Patent: WO2003/91196,2003,A1 .Location in patent: Page/Page column 18

27
[ 875932-94-8 ]
[ 19740-72-8 ]
[ 875932-95-9 ]

Yield	Reaction Conditions	Operation in experiment
60%	Stage #1: 4-phthalimido-5-hexenenitrile; bis(1-methylethyl) 1,2-hydrazinedicarboxylate With sodium azide; triethylamine hydrochloride In toluene at 95 - 100℃; for 18h; Stage #2: With hydrogenchloride In water	17 Example 17; 5-(3-Phthalimido-4-pantenyI)-lJfir-tetrazole (34).; The mixture of 33 and diisopropyl hydrazodicarboxylate prepared above (0.88 g, 2.6 mmol) was added to a solution of triethylamine hydrochloride (0.76 g, 8 mmol) and sodium azide (0.52 g, 8 EPO mmol) in toluene (15 mL). After 18 h of stirring at 95-100 _C, the cooled product was extracted with water (20 mL). The separated aqueous layer was acidified with 10% HCl to pH 1.5 to salt out the produced tetrazole. The formed precipitate was filtered and dried to give 34 as a light brown solid (0.44 g, 60%). 1H NMR (400 MHz5 CDCl3) £7.8 (dd, 4H, J- 35.2 Hz, 2.4 Hz) 6.22-6.29 (m, IH), 5.27 (d, IH, J= 4.4 Hz), 5.24 (d, IH, J= 3.2 Hz) 4.72 (s, IH), 3.19-3.22 (m, IH), 2.78-2.84 (m, IH), 2.62-2.71 (m, IH), 2.18-2.22 (m, IH).

Reference： [1]Current Patent Assignee: NORTHWESTERN UNIVERSITY (ILLINOIS) - WO2007/35964, 2007, A2 Location in patent: Page/Page column 9; 16-17

28
[ 842149-46-6 ]
3-cyclohexyl-3-hydroxypropyl-4-methylbenzenesulfonate [ No CAS ]
[ 936941-77-4 ]
[ 19740-72-8 ]

Yield	Reaction Conditions	Operation in experiment
	With di-isopropyl azodicarboxylate; triphenylphosphine In tetrahydrofuran at 0 - 20℃; for 53h;	18.b To a solution of the compound of Example 18(a) 3-Cyclohexyl-3- hydroxypropyl-4-methylbenzenesulfonate (1.27 g, 4.08 mmol) and the compound of intermediate VII (1.01 g, 3.60 mmol) in tetrahydrofuran (20 mL) at 00C was added triphenylphosphine (1.75 g, 6.67 mmol) and DIAD (1.5 mL, 7.74 mmol). The reaction was allowed to warm to ambient temperature. After 2 days, additional triphenylphosphine (1.65 g, 6.29 mmol) and DIAD (0.80 mL, 4.13 mmo) were added. After an additional 5 h at ambient temperatures, the solvent was removed under reduced pressure. Flash chromatography (EtOAc/hexanes, silica gel) gave 3.07 g of the desired material. This was contaminated with bis(1 -methylethyl) 1 ,2- hydrazinedicarboxylate but was used without additional purification in the next step. MS (ES+) m/z 575.4 (M+H)+.

Reference： [1]Current Patent Assignee: GLAXOSMITHKLINE PLC - WO2007/58852, 2007, A2 Location in patent: Page/Page column 64

29
[ 87-65-0 ]
[ 2446-83-5 ]
[ 19740-72-8 ]
[ 3217-15-0 ]