Carbon dioxide methanol → Methyl((3S,4S)-1-(3-amino-2-chloro-5-cyanophenyl)-3-((tert-butyldimethylsilyl)oxy)piperidin-4-yl)carbamate

HRID 921647Notes

Reaction equation

HRID 921647 reaction equation
[NH2:1][C:2]1[C:3]([Cl:29])=[C:4]([N:10]2[CH2:15][CH2:14][C@@H:13]([NH:16][C:17](=[O:20])[O:18][CH3:19])[C@H:12]([O:21][Si:22]([C:25]([CH3:28])([CH3:27])[CH3:26])([CH3:24])[CH3:23])[CH2:11]2)[CH:5]=[C:6]([C:8]#[N:9])[CH:7]=1.C(=O)=O.CO>>[NH2:1][C:2]1[C:3]([Cl:29])=[C:4]([N:10]2[CH2:15][CH2:14][C@H:13]([NH:16][C:17](=[O:20])[O:18][CH3:19])[C@@H:12]([O:21][Si:22]([C:25]([CH3:27])([CH3:26])[CH3:28])([CH3:23])[CH3:24])[CH2:11]2)[CH:5]=[C:6]([C:8]#[N:9])[CH:7]=1

Participants

3

Reactant 2

HCID 21973728Carbon dioxide methanolHCID 131732376(+/-)-methyl ((3R,4R)-1-(3-amino-2-chloro-5-cyanophenyl)-3-((tert-butyl dimethylsilyl)oxy)piperidin-4-yl)carbamate

Product 1

HCID 89919054Methyl((3S,4S)-1-(3-amino-2-chloro-5-cyanophenyl)-3-((tert-butyldimethylsilyl)oxy)piperidin-4-yl)carbamateYield 43.8%

Procedure

(+/−)-methyl ((3R,4R)-1-(3-amino-2-chloro-5-cyanophenyl)-3-((tert-butyl dimethylsilyl)oxy) piperidin-4-yl)carbamate (Example 171E, 927 mg, 2.112 mmol) was separated by chiral SFC (Berger SFC MGIII, Column: Lux Cel-4 25×3 cm ID, 5 μm; Flow rate: 85.0 mL/min; Mobile Phase: 85/15 CO2/methanol; Detector Wavelength: 220 nm). Methyl ((3S,4S)-1-(3-amino-2-chloro-5-cyanophenyl)-3-((tert-butyldimethylsilyl)oxy)piperidin-4-yl)carbamate (406 mg) was obtained as a white foaming solid. The enantiomeric purity of each fraction was estimated to be greater than 99.5%.

Sources & evidence

ORD record
ord-7c6ef82f238e4a58b2b2989e6f2da236
Source dataset
uspto-grants-2016_03
Patent number
US09273057B2

Reaction notes

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