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

HRID 515695Notes

Reaction equation

HRID 515695 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, and filtered through Celite®. The filtrate was extracted with ethyl acetate. The combined organics were dried and concentrated, and the residue was purified by silica gel column chromatography to give the title compound (280 mg) as a colorless oil. LCMS m/z=301.4. 1H NMR (400 MHz, CDCl3) δ ppm 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, 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 silica gel column chromatography

Sources & evidence

ORD record
ord-2da0fb43eaa849ad88a53d22fcaa5c0d
Source dataset
uspto-grants-2015_08
Patent number
US09108969B2

Reaction notes

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