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

HRID 909010Notes

Reaction equation

HRID 909010 reaction equation
[Cl:1][C:2]1[CH:3]=[C:4](/[CH:8]=[N:9]/[CH3:10])[CH:5]=[CH:6][CH:7]=1.[Cl:11][C:12]1[CH:17]=[CH:16][C:15](/[C:18](=[CH:21]/[CH2:22][C:23]([CH3:26])([CH3:25])[CH3:24])/[C:19]#[N:20])=[C:14]([F:27])[CH:13]=1.[OH-].[K+]>CS(C)=O.O>[Cl:1][C:2]1[CH:3]=[C:4]([CH:8]2[C:18]([C:15]3[CH:16]=[CH:17][C:12]([Cl:11])=[CH:13][C:14]=3[F:27])([C:19]#[N:20])[CH:21]([CH2:22][C:23]([CH3:26])([CH3:25])[CH3:24])[CH2:10][NH:9]2)[CH:5]=[CH:6][CH:7]=1

Participants

6

Reactant 3

HCID 14797Potassium HydroxideHCID 58222872(Z)-2-(4-chloro-2-fluoro-phenyl)-5,5-dimethyl-hex-2-enenitrileHCID 178482757HCID 178482757, compound

Product 1

HCID 67095616rac-(2S,3S,4S)-2-(3-chloro-phenyl)-3-(4-chloro-2-fluoro-phenyl)-4-(2,2-dimethyl-propyl)-pyrrolidine-3-carbonitrileYield 36.1%

Reagents, catalysts & solvents 2

HCID 679Dimethyl SulfoxideSolventHCID 962WaterSolvent

Procedure

To a solution of [1-(3-chloro-phenyl)-meth-(E)-ylidene]-methyl-amine (0.77 g, 5.00 mmol) and (Z)-2-(4-chloro-2-fluoro-phenyl)-5,5-dimethyl-hex-2-enenitrile (1.72 g, 5.00 mmol) in DMSO (5 mL) was added KOH powder (0.56 g, 10.00 mmol) in one portion. The mixture was stirred at rt overnight. The reaction mixture was diluted with water and extracted with EtOAc three times (3×50 mL). The combined organic layers were washed with water and brine and dried over Na2SO4, and concentrated. The residue was purified by flash column (SiO2, 1%-15% of EtOAc in hexanes) after concentration to give rac-(2S,3S,4S)-2-(3-chloro-phenyl)-3-(4-chloro-2-fluoro-phenyl)-4-(2,2-dimethyl-propyl)-pyrrolidine-3-carbonitrile (0.73 g, 36.1%); HRMS (ES+) m/z Calcd for C22H23Cl2FN2+H [(M+H)+]: 405.1295, found: 405.1292, rac-(2S,3S,4R)-4-(4-chloro-2-fluoro-phenyl)-2-(3-chloro-phenyl)-3-(2,2-dimethyl-propyl)-pyrrolidine (0.0.42 g, 20.8%); HRMS (ES+) m/z Calcd for C22H23Cl2FN2+H [(M+H)+]: 405.1295, found: 405.1294, and (2S,3R,4R)-4-(4-chloro-2-fluoro-phenyl)-2-(3-chloro-phenyl)-3-(2,2-dimethyl-propyl)-pyrrolidine (0.42 g, 20.8%); HRMS (ES+) m/z Calcd for C22H23Cl2FN2+H [(M+H)+]: 405.1295, found: 405.1294.

Workup

  1. extractionextracted with EtOAc three times (3×50 mL)
  2. washThe combined organic layers were washed with water and brine
  3. dry with materialdried over Na2SO4
  4. concentrationconcentrated
  5. customThe residue was purified by flash column (SiO2, 1%-15% of EtOAc in hexanes)
  6. concentrationafter concentration

Sources & evidence

ORD record
ord-f9575774c88b4ca69df0166e271fdb1a
Source dataset
uspto-grants-2011_09
Patent number
US08017607B2

Reaction notes

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