Phosphate → HCID 72950366, compound

Participants

Reaction Steps

A suspension of racemic ethyl 3-amino-3-(3-(2-hydroxypropan-2-yl)-5-(trifluoromethyl)phenyl)propanoate hydrochloride (Example J) (540.4 mg, 1.52 mmol) in water (2.0 mL) was basified with 2.5 N NaOH solution (pH 12) by drop wise addition to give a dirty pink oily residue. The pH of the aqueous phase was adjusted to pH 8.20 by the addition of 50 mom KH2PO4 solution (40.0 mL). Amano Lipase PS (607.6 mg) was added to the above suspension and the reaction mixture was stirred at room temperature for 63 h to give a pale pink suspension. The reaction mixture was diluted with methyl t-butyl ether (MTBE) (50 mL) and the reaction mixture was stirred at room temperature for 30 min. After 30 min, the organic layer containing the (R)-ester was separated. Evaporation of the aqueous layer in vacuo afforded a cream gummy solid containing the (S)-acid as well as Amano Lipase and Phosphate buffer salt. LC-MS analysis of the crude residue shows the desired (S)-acid's mass: m/z 292 (M+H), m/z 314 (M+Na), and m/z 274 (M+H−H2O); Calcd for C13H16F3NO3: 291.27. The crude product was purified by reverse-phase HPLC with a gradient 10-40% CH3CN in water containing 0.05% TFA to give the desired product, after lyophilization, as a colorless lyophilized solid (324 mg) (TFA salt).

Provenance & Evidence