4-(Trifluoromethyl)benzoyl chloride → 4-Methyl-2-{4'-trifluoromethyl-5-[1-(4-trifluoromethyl-benzoyl)-piperidin-3-yl]-biphenyl-3-yl}-pentanoic acid ethyl ester

HRID 889721Notes

Reaction equation

HRID 889721 reaction equation
[CH2:1]([O:3][C:4](=[O:32])[CH:5]([C:10]1[CH:11]=[C:12]([C:22]2[CH:27]=[CH:26][C:25]([C:28]([F:31])([F:30])[F:29])=[CH:24][CH:23]=2)[CH:13]=[C:14]([CH:16]2[CH2:21][CH2:20][CH2:19][NH:18][CH2:17]2)[CH:15]=1)[CH2:6][CH:7]([CH3:9])[CH3:8])[CH3:2].[F:33][C:34]([F:45])([F:44])[C:35]1[CH:43]=[CH:42][C:38]([C:39](Cl)=[O:40])=[CH:37][CH:36]=1.C(N(C(C)C)CC)(C)C>CC#N.CCOC(C)=O>[CH2:1]([O:3][C:4](=[O:32])[CH:5]([C:10]1[CH:11]=[C:12]([C:22]2[CH:23]=[CH:24][C:25]([C:28]([F:29])([F:30])[F:31])=[CH:26][CH:27]=2)[CH:13]=[C:14]([CH:16]2[CH2:21][CH2:20][CH2:19][N:18]([C:39](=[O:40])[C:38]3[CH:42]=[CH:43][C:35]([C:34]([F:33])([F:44])[F:45])=[CH:36][CH:37]=3)[CH2:17]2)[CH:15]=1)[CH2:6][CH:7]([CH3:9])[CH3:8])[CH3:2]

Participants

6

Reactant 3

HCID 676074-(Trifluoromethyl)benzoyl chlorideHCID 81531DiisopropylethylamineHCID 576660204-Methyl-2-(5-piperidin-3-yl-4'-trifluoromethyl-biphenyl-3-yl)-pentanoic acid ethyl ester

Product 1

HCID 576659504-Methyl-2-{4'-trifluoromethyl-5-[1-(4-trifluoromethyl-benzoyl)-piperidin-3-yl]-biphenyl-3-yl}-pentanoic acid ethyl esterYield 87%

Reagents, catalysts & solvents 2

HCID 6342AcetonitrileSolventHCID 8857Ethyl AcetateSolvent

Procedure

To a solution of compound 33b, 4-Methyl-2-(5-piperidin-3-yl-4′-trifluoromethyl-biphenyl-3-yl)-pentanoic acid ethyl ester) (51 mg, 0.11 mmol) in CH3CN (5 ml) was added 4-(Trifluoromethyl)benzoyl chloride (35.6 mg, 0.17 mmol) and diisopropylethylamine (40 μl, 0.23 mmol). The reaction was microwaved at 130° C. for 10 minutes, was diluted with EtOAc and washed with brine, sat. NaHCO3, and brine, dried and filtered. Purification by silica gel chromatography (Isco) gave the desired product, (62 mg, 87%). Calcd for C34H35F6NO3 (M+H) 619.64, Found 620.4.

Workup

  1. customThe reaction was microwaved at 130° C. for 10 minutes
  2. washwashed with brine, sat. NaHCO3, and brine
  3. customdried
  4. filtrationfiltered
  5. customPurification by silica gel chromatography (Isco)

Sources & evidence

ORD record
ord-3d2dc0f17dd344338c01725bdde5f428
Source dataset
uspto-grants-2012_08
Patent number
US08252935B2

Reaction notes

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