Potassium Hydroxide → rac-(3S,4S,5S)-3,5-bis-(4-chloro-2-fluoro-phenyl)-4-(2,2-dimethyl-propyl)-pyrrolidine-3-carbonitrile

HRID 909011Notes

Reaction equation

HRID 909011 reaction equation
[Cl:1][C:2]1[CH:7]=[CH:6][C:5](/[CH:8]=[N:9]/[CH3:10])=[C:4]([F:11])[CH:3]=1.[Cl:12][C:13]1[CH:18]=[CH:17][C:16](/[C:19](=[CH:22]/[CH2:23][C:24]([CH3:27])([CH3:26])[CH3:25])/[C:20]#[N:21])=[C:15]([F:28])[CH:14]=1.[OH-].[K+]>CS(C)=O>[Cl:1][C:2]1[CH:7]=[CH:6][C:5]([CH:8]2[C:19]([C:16]3[CH:17]=[CH:18][C:13]([Cl:12])=[CH:14][C:15]=3[F:28])([C:20]#[N:21])[CH:22]([CH2:23][C:24]([CH3:27])([CH3:26])[CH3:25])[CH2:10][NH:9]2)=[C:4]([F:11])[CH:3]=1.[Cl:12][C:13]1[CH:18]=[CH:17][C:16]([C:19]2([C:20]#[N:21])[CH:22]([CH2:23][C:24]([CH3:25])([CH3:26])[CH3:27])[CH:8]([C:5]3[CH:6]=[CH:7][C:2]([Cl:1])=[CH:3][C:4]=3[F:11])[NH:9][CH2:10]2)=[C:15]([F:28])[CH:14]=1

Participants

6

Reactant 3

HCID 14797Potassium HydroxideHCID 58222872(Z)-2-(4-chloro-2-fluoro-phenyl)-5,5-dimethyl-hex-2-enenitrileHCID 178482786HCID 178482786, compound

Product 2

HCID 67095473rac-(2S,3S,4S)-2,3-bis(4-chloro-2-fluoro-phenyl)-4-(2,2-dimethyl-propyl)-pyrrolidine-3-carbonitrileYield 13.3%HCID 67095546rac-(3S,4S,5S)-3,5-bis-(4-chloro-2-fluoro-phenyl)-4-(2,2-dimethyl-propyl)-pyrrolidine-3-carbonitrileYield 19.7%

Reagents, catalysts & solvents 1

HCID 679Dimethyl SulfoxideSolvent

Procedure

In a manner similar to the method described in Example 3a, [1-(4-chloro-2-fluoro-phenyl)-meth-(E)-ylidene]-methyl-amine (3.43 g, 20.00 mmol) reacted with (Z)-2-(4-chloro-2-fluoro-phenyl)-5,5-dimethyl-hex-2-enenitrile (5.03 g, 20.00 mmol) in DMSO (30 mL) in the presence of KOH powder (5.72 g, 56.11 mmol) to give rac-(2S,3S,4S)-2,3-bis-(4-chloro-2-fluoro-phenyl)-4-(2,2-dimethyl-propyl)-pyrrolidine-3-carbonitrile (1.12 g 13.3%) and rac-(3S,4S,5S)-3,5-bis-(4-chloro-2-fluoro-phenyl)-4-(2,2-dimethyl-propyl)-pyrrolidine-3-carbonitrile (1.66 g 19.7%). HRMS (ES+) m/z Calcd for C22H22Cl2F2N2+H [(M+H)+]: 423.1201, found: 423.1200.

Sources & evidence

ORD record
ord-6ac6241a58b449b6acb9b7b6d1298844
Source dataset
uspto-grants-2011_09
Patent number
US08017607B2

Reaction notes

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