Hydrochloric Acid → HCID 89782120, compound

Participants

Reaction Conditions

Reaction Steps

Flask A: To a clear solution of (R)-4-(benzyloxy)-2-((tert-butoxycarbonyl)amino)butanoic acid (Combi-Blocks Inc, 5.01 g, 16.19 mmol) in THF (40 mL) at RT under nitrogen was added 1,1′-carbonyldiimidazole (3.94 g, 24.29 mmol) in one portion. Gas evolution observed and the reaction mixture was stirred 3 h. Flask B: To a cloudy mixture of mono-tert-butyl malonate (Sigma Aldrich, 4.99 mL, 32.4 mmol) and anhydrous magnesium chloride (Sigma Aldrich, 3.08 g, 32.4 mmol) in THF (60 mL) in a 3-necked 500 mL round-bottomed flask with a temperature probe at 2° C. was added potassium tert-butoxide (1.0M solution in THF, 32.4 mL, 32.4 mmol) slowly dropwise via addition funnel such that the temperature did not exceed 8° C. The resulting white suspension was stirred at RT for 2 h. The contents of Flask A was added to Flask B and the reaction mixture heated at 50° C. with stirring overnight (16 h). The reaction mixture was cooled to RT. The resulting white suspension was treated with 1N HCl (15 mL) to pH=7 and Et2O (60 mL) and washed with brine (30 mL), dried over anhydrous MgSO4, filtered, and concentrated affording crude (R)-tert-butyl 6-(benzyloxy)-4-((tert-butoxycarbonyl)amino)-3-oxohexanoate and (R,Z)-tert-butyl 6-(benzyloxy)-4-((tert-butoxycarbonyl)amino)-3-hydroxyhex-2-enoate (724a) as a viscous light yellow oil. m/z (ESI, +ve) 430.2 (M+Na)+.

Provenance & Evidence