Trifluoroacetic anhydride → 3-(4-Hydroxy-3-trifluoromethyl-phenyl)-2-methoxy-acrylic acid methyl ester

To a solution of sodium bis(trimethylsilyl)amide 1N (0.8 mL, 0.8 mmol) in THF (4 mL), was added dropwise methyl methoxyacetate (0.066 mL, 0.66 mmol) at −78° C. After allowing the mixture to stir for 1 hour, 4-Benzyloxy-3-trifluoromethyl-benzaldehyde (185 mL, 0.66 mmol) was added dropwise. When the addition was finished the mixture was warmed to room temperature and stirred for 3 additional hours. Trifluoroacetic anhydride (0.28 mL, 1.98 mmol) was added and the mixture was stirred at room temperature for 4 hours. The solvent was evaporated and the residue dissolved in ethyl acetate (50 mL). 10% palladium on carbon (200 mg) was added to the solution and the mixture stirred under hydrogen pressure (5 atm) for 16 hours, filtered through a pad of celite and concentrated under vacuum. The residue was chromatographed (silica gel, hexanes/ethyl acetate 4:1) to produce 3-(4 hydroxy-3-trifluoromethyl-phenyl)-2-methoxy-acrylic acid methyl ester as a white solid (72 mg, 40%). 1H-NMR ((CD3)2CO, 200.15 MHz): δ 9.65 (b, 1H), 8.02 (d, 1H, J=1.8), 7.87 (dd, 1H, J=8.4, 1.8), 7.08 (d, 1H, J=8.4), 6.90 (s, 1H), 3.77 (s, 3H), 3.75 (s, 3H).

1. additionWhen the addition
2. stirringstirred for 3 additional hours
3. stirringthe mixture was stirred at room temperature for 4 hours
4. customThe solvent was evaporated
5. dissolutionthe residue dissolved in ethyl acetate (50 mL)
6. addition10% palladium on carbon (200 mg) was added to the solution
7. stirringthe mixture stirred under hydrogen pressure (5 atm) for 16 hours
8. filtrationfiltered through a pad of celite
9. concentrationconcentrated under vacuum
10. customThe residue was chromatographed (silica gel, hexanes/ethyl acetate 4:1)

ORD record

ord-d28ae59bc54b4e4ba94a9d4f6ea5eae6

Source dataset

uspto-grants-2007_03

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US07192982B2