Triethylamine → 2-Bromo-1-{(3SR,4RS)-3-(3,4-dichloro-phenyl)-4-[(3-fluoro-4-trifluoromethyl-benzyl)-methyl-amino]-pyrrolidin-1-yl}-ethanone

HRID 910461Notes

Reaction equation

HRID 910461 reaction equation
[Br:1][CH2:2][C:3](Cl)=[O:4].[Cl:6][C:7]1[CH:8]=[C:9]([CH:14]2[CH2:18][NH:17][CH2:16][CH:15]2[N:19]([CH2:21][C:22]2[CH:27]=[CH:26][C:25]([C:28]([F:31])([F:30])[F:29])=[C:24]([F:32])[CH:23]=2)[CH3:20])[CH:10]=[CH:11][C:12]=1[Cl:13].C(N(CC)CC)C>C1COCC1>[Br:1][CH2:2][C:3]([N:17]1[CH2:16][CH:15]([N:19]([CH2:21][C:22]2[CH:27]=[CH:26][C:25]([C:28]([F:31])([F:29])[F:30])=[C:24]([F:32])[CH:23]=2)[CH3:20])[CH:14]([C:9]2[CH:10]=[CH:11][C:12]([Cl:13])=[C:7]([Cl:6])[CH:8]=2)[CH2:18]1)=[O:4]

Participants

5

Reactant 3

HCID 8471TriethylamineHCID 89602Bromoacetyl chlorideHCID 75231672[(3RS,4SR)-4-(3,4-Dichloro-phenyl)-pyrrolidin-3-yl]-(3-fluoro-4-trifluoromethyl-benzyl)-methyl-amine

Product 1

HCID 722534692-Bromo-1-{(3SR,4RS)-3-(3,4-dichloro-phenyl)-4-[(3-fluoro-4-trifluoromethyl-benzyl)-methyl-amino]-pyrrolidin-1-yl}-ethanoneYield 70%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent2×

Procedure

To a stirred solution of bromo-acetyl chloride (0.146 ml, 1.75 mmol) in THF (15 ml) at RT was added over 1 hour a solution of [(3RS,4SR)-4-(3,4-dichloro-phenyl)-pyrrolidin-3-yl]-(3-fluoro-4-trifluoromethyl-benzyl)-methyl-amine (Intermediate VIII-1, 0.70 g, 1.66 mmol) and triethyl amine (0.25 ml, 1.83 mmol) in THF (10 mL). The reaction was stirred over night, quenched by addition of an aqueous solution of NaHCO3, and the product extracted with EtOAC. Purification by flash chromatography (SiO2, EtOAc/Hx 1:1) yielded 0.63 g (70%) of the title compound as a white solid. ES-MS m/e: 542.6 (M+H+).

Workup

  1. customquenched by addition of an aqueous solution of NaHCO3
  2. extractionthe product extracted with EtOAC
  3. customPurification by flash chromatography (SiO2, EtOAc/Hx 1:1)

Sources & evidence

ORD record
ord-aec97c05467b41379da38642960924ee
Source dataset
uspto-grants-2011_09
Patent number
US08022099B2

Reaction notes

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