Methyl 2-iodo-4-(trifluoromethyl)benzoate → 2-Cyclohexyl-4-trifluoromethyl-benzoic acid methyl ester

HRID 2177514Notes

Reaction equation

HRID 2177514 reaction equation
[CH3:1][O:2][C:3](=[O:15])[C:4]1[CH:9]=[CH:8][C:7]([C:10]([F:13])([F:12])[F:11])=[CH:6][C:5]=1I.[Br-].[CH:17]1([Zn+])[CH2:22][CH2:21][CH2:20][CH2:19][CH2:18]1>C1COCC1.C1C=CC(P(C2C=CC=CC=2)[C-]2C=CC=C2)=CC=1.C1C=CC(P(C2C=CC=CC=2)[C-]2C=CC=C2)=CC=1.Cl[Pd]Cl.[Fe+2].[Cu]I>[CH3:1][O:2][C:3](=[O:15])[C:4]1[CH:9]=[CH:8][C:7]([C:10]([F:13])([F:12])[F:11])=[CH:6][C:5]=1[CH:17]1[CH2:22][CH2:21][CH2:20][CH2:19][CH2:18]1

Participants

6

Reactant 2

HCID 59438424Methyl 2-iodo-4-(trifluoromethyl)benzoateHCID 178418970HCID 178418970, compound

Product 1

HCID 594384412-Cyclohexyl-4-trifluoromethyl-benzoic acid methyl esterYield 68%

Reagents, catalysts & solvents 3

HCID 24350Copper(1+) iodide; Copper(I) iodide; Cuprous iodide; Cuprous iodide (CuI)CatalystHCID 178418228Bis(cyclopenta-1,4-dien-1-yl(diphenyl)phosphane);dichloropalladium;iron(2+)CatalystHCID 8028TetrahydrofuranSolvent

Conditions

Temperature
50 °C

Procedure

To a solution of 300 mg (0.909 mmol) 2-iodo-4-trifluoromethyl-benzoic acid methyl ester, 14.4 mg (0.0455 mmol) Pd(dppf)Cl2 and 10.6 mg (0.0545 mmol) copper (I) iodide in THF (5 ml) was added at room temperature 2.73 ml (1.364 mmol) cyclohexylzinc bromide (0.5M). The mixture was stirred for 3 hours. Then it was heated to 50° C. and stirred for 4 hours and at room temperature over night. The mixture was concentrated in vacuo and dissolved in ethyl acetate. Then it was washed twice with a 1N HCl solution, twice with a saturated sodium bicarbonate solution and once with brine. The organic layer was dried over sodium sulfate, filtered and concentrated in vacuo. The residue was purified on silica (Eluent: heptane/ethyl acetate 0 to 20%) to provide 176 mg (68%) of the title compound as a light yellow oil. MS (m/e): 286 (MH+).

Workup

  1. stirringstirred for 4 hours and at room temperature over night
  2. concentrationThe mixture was concentrated in vacuo
  3. dissolutiondissolved in ethyl acetate
  4. washThen it was washed twice with a 1N HCl solution, twice with a saturated sodium bicarbonate solution and once with brine
  5. dry with materialThe organic layer was dried over sodium sulfate
  6. filtrationfiltered
  7. concentrationconcentrated in vacuo
  8. customThe residue was purified on silica (Eluent: heptane/ethyl acetate 0 to 20%)

Sources & evidence

ORD record
ord-0e611c6426a4403380a27b13c339dc86
Source dataset
uspto-grants-2015_06
Patent number
US09067911B2

Reaction notes

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