Diisopropylethylamine → HCID 53349361, compound

Participants

Reaction Conditions

Reaction Steps

A 5 L round bottom flask was inerted and charged with HATU (199 g, 0.52 mol, 1.2 equiv), N,N-dimethylformamide (380 mL), and mixed. A solution of (R)-3-(tert-butoxycarbonyl)-2,2,4-trimethyloxazolidine-4-carboxylic acid (D3A) (133.1 g, 0.43 mol, 1 equiv), dichloromethane (870 mL), and N,N-diisopropylethylamine (155 mL, 0.88 mol, 2 equiv) was charged to the flask over 15 minutes. The resulting mixture was stirred at 18 to 23° C. for 1 hour. A solution of benzohydrazide (D6) (145 g, 0.43 mol, 1 equiv) in dichloromethane (1120 mL), and N,N-Dimethylformamide (420 mL) was charged over 15 minutes then stirred at 18 to 23° C. for 1 hour. After 1 hour, TLC indicated the reaction was complete. The mixture was concentrated, partitioned between ethyl acetate (2.5 L) and water (2.5 L). The phases were split and the aqueous extracted once more with ethyl acetate (1 L). The organic phases were combined, washed with 10% w/v sodium chloride (2×1 L), dried with magnesium sulfate, filtered over Celite, and concentrated under vacuum to afford the crude product (367 g, 146% yield). The crude material was purified using a silica-gel column (2 kg) which was eluted with 5 to 25% ethyl acetate in heptane to give the title product (270 g, 108% yield, 95.9% AUC by HPLC) as a yellow oil.

Provenance & Evidence