methyl (3R)-morpholine-3-carboxylate

Conditions: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: To a mixture of methyl (3R)-morpholine-3-carboxylate from Step A (556 mg, 3.83 mmol) and 3,5-difluorophenacyl bromide (450 mg, 1.92 mmol) in CH2Cl2 (2 mL) was added DIPEA (0.669 mL, 3.83 mmol). The reaction mixture was stirred at ambient temperature for 1 h, then concentrated in vacuo. The crude product was purified on silica gel, eluting with hexane:EtOAc—75:25, to yield the title compound. MS: m/z=300 (M+1). concentrated in vacuo The crude product was purified on silica gel eluting with hexane

Conditions: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: To a solution of (R)-morpholine-3,4-dicarboxylic acid-4-tert-butyl ester (5.00 g, 21.6 mmol) in MeOH (54 mL) was added thionyl chloride (3.16 mL, 43.2 mmol) dropwise, and the resulting mixture was heated at reflux for 16 h. The solution was cooled to ambient temperature and concentrated in vacuo. The residue was made basic with saturated aqueous NaHCO3 and extracted with CH2Cl2 (3×). The combined organic extracts were dried over Na2SO4, filtered, and concentrated in vacuo to yield the title compound. the resulting mixture was heated at reflux for 16 h concentrated in vacuo extracted with CH2Cl2 (3×) The combined organic extracts were dried over Na2SO4 filtered concentrated in vacuo