Potassium Hydroxide → tert-Butyl 4-(((4'-cyano-5-(trifluoromethyl)biphenyl-3-yl)methoxy)methyl)-4-(4-fluorophenyl)piperidine-1-carboxylate

HRID 391419Notes

Reaction equation

HRID 391419 reaction equation
Br[C:2]1[CH:3]=[C:4]([CH:28]=[C:29]([C:31]([F:34])([F:33])[F:32])[CH:30]=1)[CH2:5][O:6][CH2:7][C:8]1([C:21]2[CH:26]=[CH:25][C:24]([F:27])=[CH:23][CH:22]=2)[CH2:13][CH2:12][N:11]([C:14]([O:16][C:17]([CH3:20])([CH3:19])[CH3:18])=[O:15])[CH2:10][CH2:9]1.[C:35]([C:37]1[CH:42]=[CH:41][C:40](B(O)O)=[CH:39][CH:38]=1)#[N:36].[OH-].[K+]>O1CCCC1.[Pd].C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1>[C:35]([C:37]1[CH:42]=[CH:41][C:40]([C:2]2[CH:30]=[C:29]([C:31]([F:33])([F:34])[F:32])[CH:28]=[C:4]([CH2:5][O:6][CH2:7][C:8]3([C:21]4[CH:26]=[CH:25][C:24]([F:27])=[CH:23][CH:22]=4)[CH2:9][CH2:10][N:11]([C:14]([O:16][C:17]([CH3:20])([CH3:19])[CH3:18])=[O:15])[CH2:12][CH2:13]3)[CH:3]=2)=[CH:39][CH:38]=1)#[N:36]

Participants

6

Reactant 3

HCID 14797Potassium HydroxideHCID 27343264-Cyanophenylboronic acidHCID 58993524tert-Butyl 4-((3-bromo-5-(trifluoromethyl)benzyloxy)methyl)-4-(4-fluorophenyl)piperidine-1-carboxylate

Product 1

HCID 58993637tert-Butyl 4-(((4'-cyano-5-(trifluoromethyl)biphenyl-3-yl)methoxy)methyl)-4-(4-fluorophenyl)piperidine-1-carboxylate

Reagents, catalysts & solvents 2

HCID 11979704Tetrakis(triphenylphosphine)palladiumCatalystHCID 8028TetrahydrofuranSolvent

Conditions

Temperature
120 °C

Procedure

tert-Butyl 4-((3-bromo-5-(trifluoromethyl)benzyloxy)methyl)-4-(4-fluorophenyl)piperidine-1-carboxylate (130.0 mg, 0.24 mmol), 4-cyanophenylboronic acid (140.0 mg, 0.95 mmol), and tetrakis(triphenylphosphine) palladium(0) (37.1 mg, 0.024 mmol) were combined in dry tetrahydrofuran (3 mL) in a microwave tube and sealed. The mixture was flushed with nitrogen. To this was added potassium hydroxide (1 N in water, 0.75 mL, 0.75 mmol). The mixture was heated at 120° C. for 1 h via microwave. After cooling to room temperature, the reaction mixture was concentrated and purified by flash chromatography on silica gel (25% ethyl acetate/hexanes) to afford 61.0 mg (48%). 1H-NMR (CDCl3, 500 MHz) δ 7.74-7.76 (m, 2H), 7.67 (s, 1H), 7.57-7.60 (m, 2H), 7.41 (s, 1H), 7.40 (s, 1H), 7.29-7.32 (m, 2H), 6.98-7.02 (m, 2H), 4.47 (s, 2H), 3.71-3.74 (m, 2H), 3.43 (s, 2H), 3.01-3.06 (m, 2H), 2.14-2.17 (m, 2H), 1.82-1.88 (m, 2H), 1.42 (s, 9H). Mass spec.: 569.25 (MH)+.

Workup

  1. customsealed
  2. customThe mixture was flushed with nitrogen
  3. temperatureAfter cooling to room temperature
  4. concentrationthe reaction mixture was concentrated
  5. custompurified by flash chromatography on silica gel (25% ethyl acetate/hexanes)
  6. customto afford 61.0 mg (48%)

Sources & evidence

ORD record
ord-42de0d83e2c5445c9c8214e2d315bdec
Source dataset
uspto-grants-2013_02
Patent number
US08383821B2

Reaction notes

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