Water → 3'-(Hydroxymethyl)-5'-(trifluoromethyl)biphenyl-4-carbonitrile

HRID 391370

Reaction equation

HRID 391370 reaction equation
Br[C:2]1[CH:3]=[C:4]([CH2:12][OH:13])[CH:5]=[C:6]([C:8]([F:11])([F:10])[F:9])[CH:7]=1.[C:14]([C:16]1[CH:21]=[CH:20][C:19](B(O)O)=[CH:18][CH:17]=1)#[N:15].[OH-].[K+].O>C1COCC1.C(OCC)(=O)C.[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>[OH:13][CH2:12][C:4]1[CH:3]=[C:2]([C:19]2[CH:20]=[CH:21][C:16]([C:14]#[N:15])=[CH:17][CH:18]=2)[CH:7]=[C:6]([C:8]([F:11])([F:10])[F:9])[CH:5]=1

Participants

8

Reactant 4

HCID 962WaterHCID 14797Potassium HydroxideHCID 27343264-Cyanophenylboronic acidHCID 29919767[3-Bromo-5-(trifluoromethyl)phenyl]methanol

Product 1

HCID 589936723'-(Hydroxymethyl)-5'-(trifluoromethyl)biphenyl-4-carbonitrileYield 51%

Reagents, catalysts & solvents 3

HCID 11979704Tetrakis(triphenylphosphine)palladiumCatalystHCID 8028TetrahydrofuranSolventHCID 8857Ethyl AcetateSolvent

Conditions

Temperature
120 °C

Procedure

A solution of (3-bromo-5-(trifluoromethyl)phenyl)methanol (3.0 g, 11.8 mmol), 4-cyanophenyl boronic acid (5.2 g, 35 mmol), tetrakis(triphenylphosphine) palladium(0) (2.7 g, 2.4 mmol), and aqueous potassium hydroxide (41 mL, 1N, 41 mmol) in THF (80 mL) was degassed with nitrogen for 10 minutes and then heated at 120° C. for 18 hours. The reaction was cooled to ambient temperature and poured into water (100 mL), then was diluted with ethyl acetate (100 mL) and the layers were separated. The aqueous layer was extracted with ethyl acetate (2×20 mL) and the combined organic layers were dried with MgSO4 and evaporated. The residue was purified by chromatography on SiO2 with a gradient of ethyl acetate/hexanes of 5%-40%. The product 3′-(hydroxymethyl)-5′-(trifluoromethyl)biphenyl-4-carbonitrile (1.66 g, 51%) was obtained as a white solid. 1H-NMR (CDCl3, 400 MHz) δ 7.65-7.80 (m, 7H), 4.85 (s, 2H), 1.90 (bs, 1H). Mass spec.: 278.2 (M+H).

Workup

  1. temperatureThe reaction was cooled to ambient temperature
  2. customthe layers were separated
  3. extractionThe aqueous layer was extracted with ethyl acetate (2×20 mL)
  4. dry with materialthe combined organic layers were dried with MgSO4
  5. customevaporated
  6. customThe residue was purified by chromatography on SiO2 with a gradient of ethyl acetate/hexanes of 5%-40%

Sources & evidence

ORD record
ord-2bdd23daea614f9c8d1f158af53d56d0
Source dataset
uspto-grants-2013_02
Patent number
US08383821B2

Linked notes

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