Ethyl Acetate → Methyl 4-[4-(trifluoromethoxy)benzyl]benzoate

HRID 1496916Notes

Reaction equation

HRID 1496916 reaction equation
Br[CH2:2][C:3]1[CH:12]=[CH:11][C:6]([C:7]([O:9][CH3:10])=[O:8])=[CH:5][CH:4]=1.[F:13][C:14]([F:30])([F:29])[O:15][C:16]1[CH:21]=[CH:20][C:19](C2C=CC(O)=CC=2)=[CH:18][CH:17]=1.CCOC(C)=O>COCCOC.C([O-])([O-])=O.[K+].[K+].[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>[F:13][C:14]([F:29])([F:30])[O:15][C:16]1[CH:21]=[CH:20][C:19]([CH2:2][C:3]2[CH:12]=[CH:11][C:6]([C:7]([O:9][CH3:10])=[O:8])=[CH:5][CH:4]=2)=[CH:18][CH:17]=1

Participants

7

Reactant 3

HCID 8857Ethyl AcetateHCID 256687Methyl 4-(bromomethyl)benzoateHCID 120087344-(4-Trifluoromethoxyphenyl)phenol

Product 1

HCID 66707520Methyl 4-[4-(trifluoromethoxy)benzyl]benzoateYield 69.3%

Reagents, catalysts & solvents 3

HCID 11979704Tetrakis(triphenylphosphine)palladiumCatalystHCID 80711,2-DimethoxyethaneSolventHCID 11430Potassium CarbonateSolvent

Conditions

Temperature
105 °C

Procedure

A solution of methyl 4-(bromomethyl)benzoate (93) (0.23 mL, 1.0 mmol) and 4-(trifluoromethoxy)phenylboronic acid (44) (0.24 g, 1.1 mmol) in DME (3 mL) and 2M aqueous K2CO3 (1 mL) was degassed, then treated with tetrakis(triphenylphosphine) palladium (58 mg, 50 μmol). The reaction mixture was stirred under N2 at 105° C. for 24 h, and then EtOAc (250 mL) was added. The organic layer was washed with water, the aqueous layer was re-extracted with EtOAc (100 mL), and the combined organic layers were washed with brine, dried (Na2SO4) and concentrated under reduced pressure. The residue was chromatographed on silica gel, eluting with petroleum ether/EtOAc (9:1), to give methyl 4-[4-(trifluoromethoxy)benzyl]benzoate (94) (215 mg, 68%) as a colourless oil; 1H NMR (CDCl3) δ 7.98-7.94 (m, 2H), 7.26-7.22 (m, 2H), 7.20-7.12 (m, 4H), 4.03 (s, 2H), 3.90 (s, 3H); HREIMS calcd for C16H13F3O3 m/z (TO 310.0817, found 310.0815.

Workup

  1. washThe organic layer was washed with water
  2. extractionthe aqueous layer was re-extracted with EtOAc (100 mL)
  3. washthe combined organic layers were washed with brine
  4. dry with materialdried (Na2SO4)
  5. concentrationconcentrated under reduced pressure
  6. customThe residue was chromatographed on silica gel
  7. washeluting with petroleum ether/EtOAc (9:1)

Sources & evidence

ORD record
ord-06c7afba29484374a918b65d174025ba
Source dataset
uspto-grants-2015_12
Patent number
US09198913B2

Reaction notes

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