Potassium Carbonate → benzyl tetrahydro-3-oxo-1H-oxazolo[3,4-a]pyrazine-7(3H)-carboxylate

Participants

Reaction Conditions

Reaction Steps

1,4-Di((benzyloxy)carbonyl)piperazine-2-carboxylic acid (18.9 g, 47.4 mmol) was dissolved in THF (200 mL), and borane-THF complex (1.0 M solution in THF, 100 mL, 100 mmol) was added over about 15 min. Upon complete addition, the reaction mixture was heated to 50° C. After 3 h, the reaction mixture was allowed to cool to rt and was slowly quenched by the dropwise addition of MeOH. After gas evolution ceased, the reaction mixture was heated to 50° C. for 1 h. Upon cooling to rt, the reaction mixture was concentrated under reduced pressure. The material was dissolved in EtOH (200 mL) and K2CO3 (6.9 g, 49.9 mmol) was added. The reaction mixture was heated to 70° C. overnight. Upon cooling to rt, the reaction mixture was concentrated under reduced pressure, diluted with H2O (200 mL) and extracted with EtOAc (3×200 mL). The combined organics were dried over Na2SO4, filtered, and concentrated under reduced pressure. The material was purified by column chromatography (10 to 40% EtOAc in Hexanes gradient) to give 10.26 g (78%) of the desired product as a white solid. An additional 0.452 g (3%) of the desired product was isolated from impure chromatography fractions by recrystallization from methyl tert-butyl ether. LC-MS: RT=7.848 min; [M+Na]+=299.1.

Provenance & Evidence