Potassium Carbonate → 5-chloro-2-methylamino-N-[4-(3,3,3-trifluoro-2-hydroxy-propoxy)-benzyl]-N-[2-(3-trifluoromethyl-phenyl)-ethyl]-benzamide

HRID 2244385Notes

Reaction equation

HRID 2244385 reaction equation
[Cl:1][C:2]1[CH:3]=[CH:4][C:5]([NH:31][CH3:32])=[C:6]([CH:30]=1)[C:7]([N:9]([CH2:22][C:23]1[CH:28]=[CH:27][C:26]([OH:29])=[CH:25][CH:24]=1)[CH2:10][CH2:11][C:12]1[CH:17]=[CH:16][CH:15]=[C:14]([C:18]([F:21])([F:20])[F:19])[CH:13]=1)=[O:8].Br[CH2:34][CH:35]([OH:40])[C:36]([F:39])([F:38])[F:37].C(=O)([O-])[O-].[K+].[K+]>CN(C=O)C.O.[Cl-].[Na+].O>[Cl:1][C:2]1[CH:3]=[CH:4][C:5]([NH:31][CH3:32])=[C:6]([CH:30]=1)[C:7]([N:9]([CH2:22][C:23]1[CH:24]=[CH:25][C:26]([O:29][CH2:34][CH:35]([OH:40])[C:36]([F:39])([F:38])[F:37])=[CH:27][CH:28]=1)[CH2:10][CH2:11][C:12]1[CH:17]=[CH:16][CH:15]=[C:14]([C:18]([F:21])([F:19])[F:20])[CH:13]=1)=[O:8]

Participants

7

Reactant 3

HCID 11430Potassium CarbonateHCID 2206323-Bromo-1,1,1-Trifluoro-2-PropanolHCID 687030505-chloro-N-(4-hydroxy-benzyl)-2-methylamino-N-[2-(3-trifluoromethyl-phenyl)-ethyl]-benzamide

Product 1

HCID 866152415-chloro-2-methylamino-N-[4-(3,3,3-trifluoro-2-hydroxy-propoxy)-benzyl]-N-[2-(3-trifluoromethyl-phenyl)-ethyl]-benzamideYield 59.3%

Reagents, catalysts & solvents 3

HCID 962WaterSolventHCID 6228DimethylformamideSolventHCID 57417360Sodium chloride; waterSolvent

Procedure

A suspension of 80 mg (0.17 mmol) of 5-chloro-N-(4-hydroxy-benzyl)-2-methylamino-N-[2-(3-trifluoromethyl-phenyl)-ethyl]-benzamide, 40 mg (0.21 mmol) 3-bromo-1,1,1-trifluoro-2-propanol and 57 mg (0.41 mmol) of potassium carbonate in 3 ml DMF was stirred at RT for 65 hours. The reaction mixture was then diluted with 15 ml water and 15 ml brine, and extracted twice with ethylacetate. The combined organic layers were washed with brine, dried over magnesium sulfate, filtered and concentrated in vacuo. The residue was purified by column chromatography (silica gel; DCM/EtOAc 97:3) to give 58 mg of 5-chloro-2-methylamino-N-[4-(3,3,3-trifluoro-2-hydroxy-propoxy)-benzyl]-N-[2-(3-trifluoromethyl-phenyl)-ethyl]-benzamide (55%) as a light yellow viscous oil. MS (ISP) 575.3 (M+H)+.

Workup

  1. extractionextracted twice with ethylacetate
  2. washThe combined organic layers were washed with brine
  3. dry with materialdried over magnesium sulfate
  4. filtrationfiltered
  5. concentrationconcentrated in vacuo
  6. customThe residue was purified by column chromatography (silica gel; DCM/EtOAc 97:3)

Sources & evidence

ORD record
ord-25c157ce7a6943a09cf07b3505911f27
Source dataset
uspto-grants-2010_03
Patent number
US07678818B2

Reaction notes

Loading…