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

HRID 1806919Notes

Reaction equation

HRID 1806919 reaction equation
[CH2:1]([O:8][C:9](=[O:24])[C:10]([CH3:23])([CH3:22])[CH2:11]/[CH:12]=[N:13]/[CH2:14][C:15]([O:17][C:18]([CH3:21])([CH3:20])[CH3:19])=[O:16])[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.[Cl:25][C:26]1[C:27]([F:44])=[C:28](/[CH:32]=[C:33](/[C:36]2[CH:41]=[CH:40][C:39]([Cl:42])=[CH:38][C:37]=2[F:43])\[C:34]#[N:35])[CH:29]=[CH:30][CH:31]=1.C(N(CC)CC)C.C1CCN2C(=NCCC2)CC1>ClCCl.C(O)(C)(C)C>[C:18]([O:17][C:15]([CH:14]1[CH:32]([C:28]2[CH:29]=[CH:30][CH:31]=[C:26]([Cl:25])[C:27]=2[F:44])[C:33]([C:36]2[CH:41]=[CH:40][C:39]([Cl:42])=[CH:38][C:37]=2[F:43])([C:34]#[N:35])[CH:12]([CH2:11][C:10]([C:9]([O:8][CH2:1][C:2]2[CH:3]=[CH:4][CH:5]=[CH:6][CH:7]=2)=[O:24])([CH3:23])[CH3:22])[NH:13]1)=[O:16])([CH3:19])([CH3:21])[CH3:20]

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 178451254HCID 178451254, compound

Product 1

HCID 67297241rac-(2R,3S,4R,5S)-5-(2-benzyloxycarbonyl-2-methyl-propyl)-3-(3-chloro-2-fluoro-phenyl)-4-(4-chloro-2-fluoro-phenyl)-4-cyano-pyrrolidine-2-carboxylic acid tert-butyl esterYield 19%

Reagents, catalysts & solvents 2

HCID 6344DichloromethaneSolventHCID 6386tert-ButanolSolvent

Procedure

In a manner similar to the method described in Example 100b, 4-[(E)-tert-butoxycarbonylmethylimino]-2,2-dimethyl-butyric acid benzyl ester prepared in Example 103a (4.1 g, 12.3 mmol) was reacted with (Z)-3-(3-chloro-2-fluoro-phenyl)-2-(4-chloro-2-fluoro-phenyl)-acrylonitrile (2.5 g, 8 mmol) prepared in Example 52a, AgF (1.55 g, 12.3 mmol), and triethylamine (2.5 g, 24 mmol) in dichloromethane (150 mL) at room temperature for 18 h, followed by the reaction with DBU (4 ml) in tert-butanol (40 mL) at 100° C. for 4 h to give rac-(2R,3S,4R,5S)-5-(2-benzyloxycarbonyl-2-methyl-propyl)-3-(3-chloro-2-fluoro-phenyl)-4-(4-chloro-2-fluoro-phenyl)-4-cyano-pyrrolidine-2-carboxylic acid tert-butyl ester as a light yellow gum (0.98 g, 19%).

Sources & evidence

ORD record
ord-dc2e8d1f555e4595ba96a616a97bce7b
Source dataset
uspto-grants-2013_01
Patent number
US08354444B2

Reaction notes

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