Potassium tert-butoxide → Tert-butyl 4-(2-bromo-4-fluorophenyl)-4-(((4'-cyano-5-(trifluoromethyl)biphenyl-3-yl)methoxy)methyl)piperidine-1-carboxylate

HRID 391373

Reaction equation

HRID 391373 reaction equation
CC(C)([O-])C.[K+].[Br:7][C:8]1[CH:13]=[C:12]([F:14])[CH:11]=[CH:10][C:9]=1[C:15]1([CH2:28][OH:29])[CH2:20][CH2:19][N:18]([C:21]([O:23][C:24]([CH3:27])([CH3:26])[CH3:25])=[O:22])[CH2:17][CH2:16]1.Br[CH2:31][C:32]1[CH:33]=[C:34]([C:42]2[CH:47]=[CH:46][C:45]([C:48]#[N:49])=[CH:44][CH:43]=2)[CH:35]=[C:36]([C:38]([F:41])([F:40])[F:39])[CH:37]=1>C1COCC1>[Br:7][C:8]1[CH:13]=[C:12]([F:14])[CH:11]=[CH:10][C:9]=1[C:15]1([CH2:28][O:29][CH2:31][C:32]2[CH:33]=[C:34]([C:42]3[CH:47]=[CH:46][C:45]([C:48]#[N:49])=[CH:44][CH:43]=3)[CH:35]=[C:36]([C:38]([F:39])([F:40])[F:41])[CH:37]=2)[CH2:20][CH2:19][N:18]([C:21]([O:23][C:24]([CH3:25])([CH3:26])[CH3:27])=[O:22])[CH2:17][CH2:16]1

Participants

5

Reactant 3

HCID 23665647Potassium tert-butoxideHCID 589934903'-(Bromomethyl)-5'-(trifluoromethyl)biphenyl-4-carbonitrileHCID 58993626Tert-butyl 4-(2-bromo-4-fluorophenyl)-4-(hydroxymethyl)piperidine-1-carboxylate

Product 1

HCID 58993540Tert-butyl 4-(2-bromo-4-fluorophenyl)-4-(((4'-cyano-5-(trifluoromethyl)biphenyl-3-yl)methoxy)methyl)piperidine-1-carboxylateYield 68.1%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

Potassium tert-butoxide (266 mg, 2.37 mmol) was added to a 0° C. solution of tert-butyl 4-(2-bromo-4-fluorophenyl)-4-(hydroxymethyl)piperidine-1-carboxylate (460 mg, 1.18 mmol) and 3′-(bromomethyl)-5′-(trifluoromethyl)biphenyl-4-carbonitrile (524 mg, 1.54 mmol) in THF (10 mL) and was allowed to warm to ambient temperature and stir for 24 hours. The solvent was evaporated and the residue was purified by chromatography on SiO2 with a gradient of ethyl acetate/hexanes from 5% to 40%. The product tert-butyl 4-(2-bromo-4-fluorophenyl)-4-(((4′-cyano-5-(trifluoromethyl)biphenyl-3-yl)methoxy)methyl)piperidine-1-carboxylate (520 mg, 68%) was isolated as a clear syrup. 1H-NMR (CDCl3, 400 MHz) δ 7.75 (d, J=8.3 Hz, 2H), 7.67 (s, 1H), 7.58 (d, J=8.3 Hz, 2H), 7.36 (m, 3H), 7.22 (m, 1H), 6.99 (m, 1H), 4.49 (s, 2H), 3.94 (s, 2H), 3.57 (m, 1H), 3.24 (m 1H), 2.48 (m, 2H), 2.05 (m, 2H), 1.42 (s, 9H). Mass spec.: 647.2 (M+H).

Workup

  1. customThe solvent was evaporated
  2. customthe residue was purified by chromatography on SiO2 with a gradient of ethyl acetate/hexanes from 5% to 40%

Sources & evidence

ORD record
ord-26e4603efb0b4b56b94b6c7a9666201b
Source dataset
uspto-grants-2013_02
Patent number
US08383821B2

Linked notes

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