Diisopropylethylamine → 2-{5-[1-(3-Fluoro-5-trifluoromethyl-benzyl)-piperidin-3-yl]-4'-trifluoromethyl-biphenyl-3-yl}-4-methyl-pentanoic acid

HRID 889725Notes

Reaction equation

HRID 889725 reaction equation
C([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])C.[F:33][C:34]1[CH:35]=[C:36]([CH:39]=[C:40]([C:42]([F:45])([F:44])[F:43])[CH:41]=1)[CH2:37]Br.C(N(C(C)C)CC)(C)C>CC#N.CCOC(C)=O>[F:33][C:34]1[CH:35]=[C:36]([CH:39]=[C:40]([C:42]([F:45])([F:44])[F:43])[CH:41]=1)[CH2:37][N:18]1[CH2:19][CH2:20][CH2:21][CH:16]([C:14]2[CH:15]=[C:10]([CH:5]([CH2:6][CH:7]([CH3:9])[CH3:8])[C:4]([OH:32])=[O:3])[CH:11]=[C:12]([C:22]3[CH:23]=[CH:24][C:25]([C:28]([F:31])([F:30])[F:29])=[CH:26][CH:27]=3)[CH:13]=2)[CH2:17]1

Participants

6

Reactant 3

HCID 81531DiisopropylethylamineHCID 27375751-(Bromomethyl)-3-fluoro-5-(trifluoromethyl)benzeneHCID 576660204-Methyl-2-(5-piperidin-3-yl-4'-trifluoromethyl-biphenyl-3-yl)-pentanoic acid ethyl ester

Product 1

HCID 252707742-{5-[1-(3-Fluoro-5-trifluoromethyl-benzyl)-piperidin-3-yl]-4'-trifluoromethyl-biphenyl-3-yl}-4-methyl-pentanoic acidYield 85%

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 (44.6 mg, 0.10 mmol) in CH3CN (5 ml) was added 3-Fluoro-5-trifluoromethyl benzyl bromide) (77 mg, 0.3 mmol) and diisopropylethylamine (35 μl, 0.20 mmol). The reaction was microwaved at 130° C. for 10 minutes, then diluted with EtOAc and washed with brine, sat. NaHCO3, and brine, dried and filtered. Purification by silica gel chromatography (Isco) gave the desired product, (53 mg, 85%). Calcd for C34H36F7N1O2 (M+H) 623.64, Found 624.3

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-74978780dbc043d08aa6ccc46d50ca68
Source dataset
uspto-grants-2012_08
Patent number
US08252935B2

Reaction notes

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