Methanol → Methyl N-{4-[2,2,2-trifluoro-1-hydroxy-1-(trifluoromethyl)ethyl]phenyl}-phenylalaninate

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Reaction Steps

Sulfuric acid (1 mL) was added to the product of step 1 (1.4 g, 3.65 mmol) and the resulting mixture stirred at ambient temperature for 2.5 h. Methanol (2 mL) was added and the solution heated at reflux for 3 h. The solution was cooled to room temperature and 1 M NaOH added until a pH=8 was reached. The solution was extracted with ethyl acetate and the combined organics washed with brine, dried (Na2SO4) and concentrated in vacuo. Purification by reverse phase HPLC using a gradient elution of 60:40 H2O/TFA:CH3CN to 0:100 H2O/TFA:CH3CN at 254 nm afforded the title compound as a yellow oil (768 mg, 50%). 1H NMR (CDCl3) δ 7.47 (d, 2H), 7.32-7.25 (m, 3H), 7.14 (m, 2H), 6.61 (d, 2H), 4.38 (t, 1H), 3.70 (s, 3H), 3.25 (brs, 1H), 3.17 (dd, 1H), 3.11 (dd, 1H). MS (ES+) m/z422 (MH+). Anal. Calc. for C19H17NO3F6+0.1H2O: C, 53.93; H, 4.10; N, 3.31. Found: C, 53.73; H, 3.92; N, 3.54.

Provenance & Evidence