Citric Acid → HCID 89415622, compound

Participants

Reaction Conditions

Reaction Steps

To a slurry of 2,3-dichloroquinoxaline 11 (100 g, 0.437 mol) and N-Boc-4-trans-hydroxy-L-proline methyl ester (12, 118 g, 0.48 mol) in DMAc (500 ml, KF<150) at ambient temperature was added DBU (86 g, 0.568 mol). The slurry was agitated at 40-45° C. for ˜35 hours. The batch was then cooled to 15° C. Ethyl acetate (1.2 L) followed by citric acid (10%, 504 mL, 162 mmol) was added while the internal temperature was maintained <25° C. The organic phase was washed with a solution of 10% citric acid (200 mL) and water (200 mL) followed by water (400 mL×2). The organic phase was azeotropically dried and solvent switched to MeCN at a final volume of ˜880 mL. MeSO3H (36 mL, 0.555 mol) was added and the reaction mixture was aged at 40° C. for ˜16 hours. To the reaction slurry was added MTBE (1.05 L) dropwise over 2 hours at 35° C. Then, the batch was further cooled to 0-5° C. and aged for 2-3 hours before filtration. The wet cake was displacement washed with 30% MeCN in MTBE (600 mL×2), and vacuum oven dried at 40° C. to give the product 14.

Provenance & Evidence