Synthesis
Example 59a Single Enantiomeric Isomer; R Configuration
NaHCO3 (1.0 g, 11.9 mmol) was added to a stirred aqueous suspension of (R)-4-fluorophenylglycine (1.0 g, 5.9 mmol). after 30 min, a solution of di-tert-butyl dicarbonate (1.5 g, 7.1 mmol) dissolved in tertiary butanol was slowly added dropwise. The reaction mixture was stirred overnight at room temperature. Upon completion of the reaction, the reaction mixture was diluted with water and the pH was subsequently adjusted to 4-5 with 5% aqueous citric acid.The mixture was extracted with dichloromethane (DCM), the organic layer was separated, dried over anhydrous Na2SO4 and concentrated under reduced pressure to give the title compound (R)-2-((tert-butoxycarbonyl)amino)-2-(4-fluorophenyl)acetic acid (1.6 g).
HPLC-MS (Method 17): retention time (Rt) = 2.25 min; mass spectrum (ES+): m/z = 292 [M + Na]+.
