Triethylamine → rac-(2R,3R,4R,5S)-3-(3-chloro-4-fluoro-phenyl)-4-(4-chloro-2-fluoro-phenyl)-4-cyano-5-(2,2-dimethyl-propyl)-pyrrolidine-2-carboxylic acid tert-butyl ester

HRID 1806832Notes

Reaction equation

HRID 1806832 reaction equation
[C:1]([O:5][C:6](=[O:15])[CH2:7]/[N:8]=[CH:9]/[CH2:10][C:11]([CH3:14])([CH3:13])[CH3:12])([CH3:4])([CH3:3])[CH3:2].[Cl:16][C:17]1[CH:18]=[C:19](/[CH:24]=[C:25](/[C:28]2[CH:33]=[CH:32][C:31]([Cl:34])=[CH:30][C:29]=2[F:35])\[C:26]#[N:27])[CH:20]=[CH:21][C:22]=1[F:23].C(N(CC)CC)C>ClCCl>[C:1]([O:5][C:6]([CH:7]1[CH:24]([C:19]2[CH:20]=[CH:21][C:22]([F:23])=[C:17]([Cl:16])[CH:18]=2)[C:25]([C:28]2[CH:33]=[CH:32][C:31]([Cl:34])=[CH:30][C:29]=2[F:35])([C:26]#[N:27])[CH:9]([CH2:10][C:11]([CH3:14])([CH3:13])[CH3:12])[NH:8]1)=[O:15])([CH3:4])([CH3:3])[CH3:2]

Participants

5

Reactant 3

HCID 8471TriethylamineHCID 59249591(Z)-3-(3-chloro-4-fluoro-phenyl)-2-(4-chloro-2-fluoro-phenyl)-acrylonitrileHCID 178444818HCID 178444818, compound

Product 1

HCID 67296918rac-(2R,3R,4R,5S)-3-(3-chloro-4-fluoro-phenyl)-4-(4-chloro-2-fluoro-phenyl)-4-cyano-5-(2,2-dimethyl-propyl)-pyrrolidine-2-carboxylic acid tert-butyl esterYield 24%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

In a manner similar to the method described in Example 1c, [3-methyl-but-(E)-ylideneamino]-acetic acid tert-butyl ester prepared in Example 1a (2.1 g, 10 mmol) was reacted with (Z)-3-(3-chloro-4-fluoro-phenyl)-2-(4-chloro-2-fluoro-phenyl)-acrylonitrile (2.5 g, 8 mmol) prepared in Example 69a, AgF (1.5 g, 12 mmol), and triethylamine (2.7 mL, 20 mmol) in dichloromethane (120 mL) at room temperature for 18 h to give rac-(2R,3R,4R,5S)-3-(3-chloro-4-fluoro-phenyl)-4-(4-chloro-2-fluoro-phenyl)-4-cyano-5-(2,2-dimethyl-propyl)-pyrrolidine-2-carboxylic acid tert-butyl ester as a white foam (1 g, 24%).

Sources & evidence

ORD record
ord-5fc9624409f549088dc4b7035d630775
Source dataset
uspto-grants-2013_01
Patent number
US08354444B2

Reaction notes

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