Diisopropylethylamine → N-(2-(4-chlorophenyl)-2-oxoethyl)-4,4,4-trifluoro-3-((3-(3-(trifluoromethyl)phenyl)piperidin-1-yl)methyl)butanamide

HRID 1051399

Reaction equation

HRID 1051399 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.CN(C(ON1N=NC2C=CC=NC1=2)=[N+](C)C)C.F[P-](F)(F)(F)(F)F.Cl.[NH2:52][CH2:53][C:54]([C:56]1[CH:61]=[CH:60][C:59]([Cl:62])=[CH:58][CH:57]=1)=[O:55].CCN(C(C)C)C(C)C>C(OCC)(=O)C.CN(C=O)C>[Cl:62][C:59]1[CH:58]=[CH:57][C:56]([C:54](=[O:55])[CH2:53][NH:52][C:5](=[O:7])[CH2:4][CH:3]([CH2:8][N:9]2[CH2:14][CH2:13][CH2:12][CH:11]([C:15]3[CH:20]=[CH:19][CH:18]=[C:17]([C:21]([F:23])([F:24])[F:22])[CH:16]=3)[CH2:10]2)[C:2]([F:25])([F:26])[F:1])=[CH:61][CH:60]=1

Participants

7

Reactant 4

HCID 81531DiisopropylethylamineHCID 27982112-Amino-1-(4-chlorophenyl)ethan-1-one hydrochlorideHCID 9886157Methanaminium, N-((dimethylamino)(3H-1,2,3-triazolo(4,5-b)pyridin-3-yloxy)methylene)-N-methyl-, hexafluorophosphate(1-) (1:1)HCID 901035704,4,4-Trifluoro-3-((3-(3-(trifluoromethyl)phenyl)piperidin-1-yl)methyl)butanoic acid

Product 1

HCID 90133968N-(2-(4-chlorophenyl)-2-oxoethyl)-4,4,4-trifluoro-3-((3-(3-(trifluoromethyl)phenyl)piperidin-1-yl)methyl)butanamideYield 65%

Reagents, catalysts & solvents 2

HCID 6228DimethylformamideSolventHCID 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 (40 mg, 104 μmol) and HATU (39.7 mg, 104 μmol) were combined with DMF (1 ml) to give a colorless solution. After 5 min of stirring, 2-amino-1-(4-chlorophenyl)ethanone HCl (21.5 mg, 104 μmol) was added followed by drop-wise addition of DIEA (47.2 mg, 63.8 μl, 365 μmol). The reaction mixture was stirred at room temperature overnight. The reaction mixture was diluted with ethyl acetate (30 ml), washed with brine and H2O, dried over MgSO4, filtered and concentrated in vacuo to give an oil. The crude material was purified by flash chromatography (silica gel, 12 g, 0% to 50% ethyl acetate in CH2Cl2) to afford 36 mg (65%) of N-(2-(4-chlorophenyl)-2-oxoethyl)-4,4,4-trifluoro-3-((3-(3-(trifluoromethyl)phenyl)piperidin-1-yl)methyl)butanamide as an oil. MH+=535.

Workup

  1. customto give a colorless solution
  2. stirringThe reaction mixture was stirred at room temperature overnight
  3. washwashed with brine and H2O
  4. dry with materialdried over MgSO4
  5. filtrationfiltered
  6. concentrationconcentrated in vacuo
  7. customto give an oil
  8. customThe crude material was purified by flash chromatography (silica gel, 12 g, 0% to 50% ethyl acetate in CH2Cl2)

Sources & evidence

ORD record
ord-083bed640ecf407cb88d4beaddab3e7e
Source dataset
uspto-grants-2016_07
Patent number
US09388172B2

Linked notes

Loading…