Dimethylformamide → 2-(4-Chlorophenyl)-2-oxoethyl 4,4,4-trifluoro-3-((3-(3-(trifluoromethyl)-phenyl)piperidin-1-yl)methyl)butanoate

HRID 1051394Notes

Reaction equation

HRID 1051394 reaction equation
[F:1][C:2]([F:26])([F:25])[CH:3]([CH2:8][N:9]1[CH2:14][CH2:13][CH2:12][CH:11]([C:15]2[CH:20]=[CH:19][CH:18]=[C:17]([C:21]([F:24])([F:23])[F:22])[CH:16]=2)[CH2:10]1)[CH2:4][C:5]([OH:7])=[O:6].CCN(C(C)C)C(C)C.CN(C=O)C.Br[CH2:42][C:43]([C:45]1[CH:50]=[CH:49][C:48]([Cl:51])=[CH:47][CH:46]=1)=[O:44]>C(OCC)(=O)C>[F:26][C:2]([F:1])([F:25])[CH:3]([CH2:8][N:9]1[CH2:14][CH2:13][CH2:12][CH:11]([C:15]2[CH:20]=[CH:19][CH:18]=[C:17]([C:21]([F:22])([F:23])[F:24])[CH:16]=2)[CH2:10]1)[CH2:4][C:5]([O:7][CH2:42][C:43]([C:45]1[CH:50]=[CH:49][C:48]([Cl:51])=[CH:47][CH:46]=1)=[O:44])=[O:6]

Participants

6

Reactant 4

HCID 6228DimethylformamideHCID 68303p-Chlorophenacyl bromideHCID 81531DiisopropylethylamineHCID 901035704,4,4-Trifluoro-3-((3-(3-(trifluoromethyl)phenyl)piperidin-1-yl)methyl)butanoic acid

Product 1

HCID 901338472-(4-Chlorophenyl)-2-oxoethyl 4,4,4-trifluoro-3-((3-(3-(trifluoromethyl)-phenyl)piperidin-1-yl)methyl)butanoateYield 77.5%

Reagents, catalysts & solvents 1

HCID 8857Ethyl AcetateSolvent

Procedure

In a 10 mL pear-shaped flask, 4,4,4-trifluoro-3-((3-(3-(trifluoromethyl)phenyl)piperidin-1-yl)methyl)butanoic acid (50 mg, 130 μmol) and DIEA (50.6 mg, 68.3 μl, 391 μmol) were combined with DMF (2 ml) to give a colorless solution. 2-Bromo-1-(4-chlorophenyl)ethanone (60.9 mg, 261 μmol) was added and the resultant mixture was stirred at room temperature overnight. The reaction was diluted with ethyl acetate, washed with brine and H2O, dried with MgSO4, filtered and concentrated. The crude residue was purified on a silica column (100% hexane to 30% ethyl acetate/hexane eluent) to afford 54 mg (77%) of 2-(4-chlorophenyl)-2-oxoethyl 4,4,4-trifluoro-3-((3-(3-(trifluoromethyl)-phenyl)piperidin-1-yl)methyl)butanoate as an oil. MH+=536.

Workup

  1. customto give a colorless solution
  2. washwashed with brine and H2O
  3. dry with materialdried with MgSO4
  4. filtrationfiltered
  5. concentrationconcentrated
  6. customThe crude residue was purified on a silica column (100% hexane to 30% ethyl acetate/hexane eluent)

Sources & evidence

ORD record
ord-3649333ec4b14c598eb858ec9caf8eb6
Source dataset
uspto-grants-2016_07
Patent number
US09388172B2

Reaction notes

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