Methyl 4-chloro-3-(trifluoromethyl)benzoate → Methyl 4-(cyclohexylmethyl)-3-(trifluoromethyl)benzoate

HRID 2040555Notes

Reaction equation

HRID 2040555 reaction equation
Cl[C:2]1[CH:11]=[CH:10][C:5]([C:6]([O:8][CH3:9])=[O:7])=[CH:4][C:3]=1[C:12]([F:15])([F:14])[F:13].[Br-].[CH:17]1([CH2:23][Zn+])[CH2:22][CH2:21][CH2:20][CH2:19][CH2:18]1>C1COCC1.CC(C)([P](C(C)(C)C)([Pd][P](C(C)(C)C)(C(C)(C)C)C(C)(C)C)C(C)(C)C)C>[CH:17]1([CH2:23][C:2]2[CH:11]=[CH:10][C:5]([C:6]([O:8][CH3:9])=[O:7])=[CH:4][C:3]=2[C:12]([F:15])([F:14])[F:13])[CH2:22][CH2:21][CH2:20][CH2:19][CH2:18]1

Participants

5

Reactant 2

HCID 14148738Methyl 4-chloro-3-(trifluoromethyl)benzoateHCID 178419774HCID 178419774, compound

Product 1

HCID 67211598Methyl 4-(cyclohexylmethyl)-3-(trifluoromethyl)benzoateYield 93.2%

Reagents, catalysts & solvents 2

HCID 178418851HCID 178418851, compoundCatalystHCID 8028TetrahydrofuranSolvent

Procedure

To a stirred solution of methyl 4-chloro-3-(trifluoromethyl)benzoate (238 mg, 1.0 mmol) and bis(tri-t-butylphosphine)palladium (0) (51 mg, 0.10 mmol) in THF (2 mL) was added (cyclohexylmethyl)zinc(II) bromide (6 mL, 3.00 mmol) at room temperature. The reaction mixture was heated at reflux for 2 h, quenched with saturated NaHCO3 solution, filtered through Celite. The filtrate was extracted with ethyl acetate. The combined organics were dried and concentrated, and the residue was purified by column chromatography to give the title compound (280 mg) as colorless oil. LCMS m/z=301.4 [M+H]+. 1H NMR (400 MHz, CDCl3) δ 0.96-1.06 (m, 2H), 1.14-1.22 (m, 3H), 1.62-1.72 (m, 6H), 2.71 (d, J=6.7 Hz, 2H), 3.94 (s, 3H), 7.39 (d, J=8.1 Hz, 1H), 8.10 (dd, J=8.0 and 1.5 Hz, 1H), 8.30 (d, J=1.4 Hz, 1H).

Workup

  1. temperatureThe reaction mixture was heated
  2. temperatureat reflux for 2 h
  3. customquenched with saturated NaHCO3 solution
  4. filtrationfiltered through Celite
  5. extractionThe filtrate was extracted with ethyl acetate
  6. customThe combined organics were dried
  7. concentrationconcentrated
  8. customthe residue was purified by column chromatography

Sources & evidence

ORD record
ord-d7dd3938a6b243748545ecac7b8b6767
Source dataset
uspto-grants-2013_11
Patent number
US08580841B2

Reaction notes

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