HCID 22851707, compound → 2(S)-acetamido-3(S)-methoxycarbonyl-4(R)-pentanolide

Participants

Reaction Steps

169.2 g of (R)-2-acetamido-3-methoxycarbonyl-2-penten-4-olide are dissolved in 800 ml of methanol, 10 g of Pd/C (5%) are added and the whole is hydrogenated for 8 hours at 30° C. and 3-5 bars. The catalyst is filtered off, washed with methanol and the filtrate is concentrated by evaporation. The ratio of the diastereoisomers of the crude product exhibited by HPLC analysis is (2S,3S,4R):(2R,3S,4R):(2S,3R,4R)=approximately 5:3:2. The proportion of the (2R,3R,4R)-diastereoisomer is less than 1%. The mixture is dissolved in 500 ml of methanol, 12 g of 1,8-diazabicyclo[5.4.0]undec-7-ene are added and the whole is stirred at room temperature for 48 hours, resulting in a mixture, 86-88% of which consists of the desired (2S,3S,4R)-diastereoisomer. The solution is concentrated, neutralised with 2N hydrochloric acid, taken up in ethyl acetate and extracted with saturated sodium chloride solution. Diastereoisomerically pure title compound is obtained by crystallisation from ethyl acetate/cyclohexane, [α]D20 =-49.5° (3% in CH3OH), m.p. 105°-106° C., IR 1787, 1740, 1689, 1510 cm-1.

Provenance & Evidence