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

HRID 1807009Notes

Reaction equation

HRID 1807009 reaction equation
[C:1]([O:5][C:6](=[O:19])[CH2:7]/[N:8]=[CH:9]/[CH2:10][C:11]([CH3:18])([CH3:17])[CH2:12][CH2:13][N:14]=[N+:15]=[N-:16])([CH3:4])([CH3:3])[CH3:2].[Cl:20][C:21]1[C:22]([F:39])=[C:23](/[CH:27]=[C:28](/[C:31]2[CH:36]=[CH:35][C:34]([Cl:37])=[CH:33][C:32]=2[F:38])\[C:29]#[N:30])[CH:24]=[CH:25][CH:26]=1.C(N(CC)CC)C.C1CCN2C(=NCCC2)CC1>ClCCl.C(O)(C)(C)C>[C:1]([O:5][C:6]([CH:7]1[CH:27]([C:23]2[CH:24]=[CH:25][CH:26]=[C:21]([Cl:20])[C:22]=2[F:39])[C:28]([C:31]2[CH:36]=[CH:35][C:34]([Cl:37])=[CH:33][C:32]=2[F:38])([C:29]#[N:30])[CH:9]([CH2:10][C:11]([CH3:18])([CH3:17])[CH2:12][CH2:13][N:14]=[N+:15]=[N-:16])[NH:8]1)=[O:19])([CH3:4])([CH3:2])[CH3:3]

Participants

7

Reactant 4

HCID 8471TriethylamineHCID 811841,8-Diazabicyclo(5.4.0)undec-7-eneHCID 59249629(Z)-3-(3-Chloro-2-fluoro-phenyl)-2-(4-chloro-2-fluoro-phenyl)-acrylonitrileHCID 178446419HCID 178446419, compound

Product 1

HCID 86640428rac-(2R,3S,4R,5S)-5-(4-azido-2,2-dimethyl-butyl)-3-(3-chloro-2-fluoro-phenyl)-4-(4-chloro-2-fluoro-phenyl)-4-cyano-pyrrolidine-2-carboxylic acid tert-butyl esterYield 36%

Reagents, catalysts & solvents 2

HCID 6344DichloromethaneSolventHCID 6386tert-ButanolSolvent

Procedure

In a manner similar to the method described in Example 100b, [5-azido-3,3-dimethyl-pent-(E)-ylideneamino]-acetic acid tert-butyl ester prepared in Example 120a (0.65 g, 2.45 mmol) was reacted with (Z)-3-(3-chloro-2-fluoro-phenyl)-2-(4-chloro-2-fluoro-phenyl)-acrylonitrile (0.76 g, 2.45 mmol) prepared in Example 52a, AgF (0.47 g, 3.7 mmol), and triethylamine (0.55 mL, 6 mmol) in dichloromethane (80 mL) at room temperature for 18 h, followed by the reaction with DBU (3 ml) in tert-butanol (3 mL) at 100° C. for 2 h to give rac-(2R,3S,4R,5S)-5-(4-azido-2,2-dimethyl-butyl)-3-(3-chloro-2-fluoro-phenyl)-4-(4-chloro-2-fluoro-phenyl)-4-cyano-pyrrolidine-2-carboxylic acid tert-butyl ester as a yellow gum (0.5 g, 36%).

Sources & evidence

ORD record
ord-1af193bb7b4f43cf9fd72130e0250f63
Source dataset
uspto-grants-2013_01
Patent number
US08354444B2

Reaction notes

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