Dichloromethane → (2R,3S,4R,5S)-5-tert-Butyl-3-(3-chloro-2-fluoro-phenyl)-4-(4-chloro-phenyl)-4-cyano-pyrrolidine-2-carboxylic acid tert-butyl ester

HRID 1806763Notes

Reaction equation

[C:1]([O:5][C:6](=[O:14])[CH2:7]/[N:8]=[CH:9]/[C:10]([CH3:13])([CH3:12])[CH3:11])([CH3:4])([CH3:3])[CH3:2].[Cl:15][C:16]1[C:17]([F:33])=[C:18](/[CH:22]=[C:23](/[C:26]2[CH:31]=[CH:30]C(Cl)=[CH:28][CH:27]=2)\[C:24]#[N:25])[CH:19]=[CH:20][CH:21]=1.C(N(CC)CC)C.Cl[CH2:42][Cl:43]>>[C:1]([O:5][C:6]([C@H:7]1[C@H:22]([C:18]2[CH:19]=[CH:20][CH:21]=[C:16]([Cl:15])[C:17]=2[F:33])[C@:23]([C:26]2[CH:27]=[CH:28][C:42]([Cl:43])=[CH:30][CH:31]=2)([C:24]#[N:25])[C@H:9]([C:10]([CH3:13])([CH3:12])[CH3:11])[NH:8]1)=[O:14])([CH3:4])([CH3:3])[CH3:2]

Participants

Reactant 4

HCID 6344Dichloromethane

HCID 8471Triethylamine

HCID 59249283(Z)-3-(3-chloro-2-fluoro-phenyl)-2-(4-chloro-phenyl)-acrylonitrile

HCID 178446417HCID 178446417, compound

Product 1

HCID 59249662(2R,3S,4R,5S)-5-tert-Butyl-3-(3-chloro-2-fluoro-phenyl)-4-(4-chloro-phenyl)-4-cyano-pyrrolidine-2-carboxylic acid tert-butyl esterYield 30%

Procedure

In a manner similar to the method described in Example 1c, [2,2-dimethyl-prop-(E)-ylideneamino]-acetic acid tert-butyl ester prepared in Example 51a (1 g, 5 mmol) was reacted with (Z)-3-(3-chloro-2-fluoro-phenyl)-2-(4-chloro-phenyl)-acrylonitrile (0.8 g, 2.7 mmol) prepared in Example 26a, AgF (1.5 g, 12 mmol), and triethylamine (2 g, 20 mmol) in dichloromethane (50 mL) at room temperature for 24 h to give (2R,3S,4R,5S)-5-tert-Butyl-3-(3-chloro-2-fluoro-phenyl)-4-(4-chloro-phenyl)-4-cyano-pyrrolidine-2-carboxylic acid tert-butyl ester as a white foam (0.4 g, 30%).

Sources & evidence

ORD record: ord-dd2cee9fe3b64a9ebf88a3a31796aaf1
Source dataset: uspto-grants-2013_01
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US08354444B2

Reaction notes

Loading…