Hydrochloric Acid → Methyl 3-(5-methyl-2-thienylamino)-4-oxopentanoate

Participants

Reaction Conditions

Reaction Steps

A slurry of 19.3 g (0.136 mol) 5-methyl-2-thiophenecarboxylic acid in 200 mL of toluene was treated with 10.9 mL (0.15 mol) of thionyl chloride. The resulting mixture was heated to 70° C. for 16 h, then concentrated in vacuo. The resulting oil was added in portions to a solution of 25.0 g (0.136 mol) of b-methylaspartic acid hydrochloride in 80 mL of pyridine at 0° C. at a rate to maintain a temperature <10° C. After the addition was complete the solution was allowed to stir at 25° C. for 1 h, treated with 50 mL of acetic anhydride and heated to 90° C. for 2 h. The mixture was then cooled to 25° C., poured into 700 mL of 1N HCl, and extracted three times with EtOAc. The combined organic phases were washed three times with 3 N HCl, once with water, once with 5% Aq NaHCO3, and finally with brine. The solution was dried (Na2SO4), then chromatographed over silica gel eluting with hexanes:EtOAc 3//2 to obtain 9.1 g (25%) of the title compound as a clear yellow oil: MS (ES+) m/e 270 (MH+).

Provenance & Evidence