4-Fluorobenzoyl chloride → N-[(3RS,4SR)-4-(4-Chloro-phenyl)-1-(4-fluoro-benzoyl)-pyrrolidin-3-yl]-4-methoxy-N-methyl-3-trifluoromethyl-benzamide

HRID 1951086Notes

Reaction equation

HRID 1951086 reaction equation
[Cl:1][C:2]1[CH:7]=[CH:6][C:5]([CH:8]2[CH2:12][NH:11][CH2:10][CH:9]2[N:13]([CH3:28])[C:14](=[O:27])[C:15]2[CH:20]=[CH:19][C:18]([O:21][CH3:22])=[C:17]([C:23]([F:26])([F:25])[F:24])[CH:16]=2)=[CH:4][CH:3]=1.[F:29][C:30]1[CH:38]=[CH:37][C:33]([C:34](Cl)=[O:35])=[CH:32][CH:31]=1.C(N(CC)C(C)C)(C)C>ClCCl.C(OCC)(=O)C>[Cl:1][C:2]1[CH:3]=[CH:4][C:5]([CH:8]2[CH2:12][N:11]([C:34](=[O:35])[C:33]3[CH:37]=[CH:38][C:30]([F:29])=[CH:31][CH:32]=3)[CH2:10][CH:9]2[N:13]([CH3:28])[C:14](=[O:27])[C:15]2[CH:20]=[CH:19][C:18]([O:21][CH3:22])=[C:17]([C:23]([F:24])([F:25])[F:26])[CH:16]=2)=[CH:6][CH:7]=1

Participants

6

Reactant 3

HCID 678794-Fluorobenzoyl chlorideHCID 81531DiisopropylethylamineHCID 67025659N-[(3RS,4SR)-4-(4-Chloro-phenyl)-pyrrolidin-3-yl]-4-methoxy-N-methyl-3-trifluoromethyl-benzamide

Product 1

HCID 67025927N-[(3RS,4SR)-4-(4-Chloro-phenyl)-1-(4-fluoro-benzoyl)-pyrrolidin-3-yl]-4-methoxy-N-methyl-3-trifluoromethyl-benzamideYield 95%

Reagents, catalysts & solvents 2

HCID 6344DichloromethaneSolventHCID 8857Ethyl AcetateSolvent

Procedure

To a solution of N-[(3RS,4SR)-4-(4-chloro-phenyl)-pyrrolidin-3-yl]-4-methoxy-N-methyl-3-trifluoromethyl-benzamide (200 mg, 0.484 mmol) in dichloromethane (2 mL) was added 4-fluorobenzoyl chloride (63 μl, 0.533 mmol) and N,N-diisopropyl ethyl amine (124 μl, 0.727 mmol). The solution was stirred for 3 h at ambient temperature. After diluting with ethyl acetate (15 mL) the solution was washed twice with water (15 mL) and brine (10 mL). The aqueous layers were extracted with ethyl acetate (15 mL) and dried over sodium sulfate. Purification by chromatography (SiO2, heptane:ethyl acetate=50:50 to 0:100) afforded the title compound (245 mg, 95%) as a light brown oil. MS m/e: 535.2 [M+H]+.

Workup

  1. washwas washed twice with water (15 mL) and brine (10 mL)
  2. extractionThe aqueous layers were extracted with ethyl acetate (15 mL)
  3. dry with materialdried over sodium sulfate
  4. customPurification by chromatography (SiO2, heptane:ethyl acetate=50:50 to 0:100)

Sources & evidence

ORD record
ord-382f6c3fdde14cbbb7e0e6b4588817f9
Source dataset
uspto-grants-2013_03
Patent number
US08404679B2

Reaction notes

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