Acetic Anhydride → HCID 57309346, compound

Participants

Reaction Conditions

Reaction Steps

A solution of 11.42 ml of acetic anhydride in 50 ml of dichloromethane is added dropwise at 0°-3° within a period of 25 minutes to a solution of 20.2 g of 2, 16.83 ml of triethylamine and 0.62 g of 4-(dimethylamino)-pyridine in 300 ml of dichloromethane. After 30 minutes,the mixture is washed twice with ice-cold 2N hydrochloric acid and twice with 10% sodium chloride solution. The aqueous phases are extracted with 100 ml of dichloromethane. The organic phases are dried over sodium sulphate and concentrated by evaporation, and the residue is dissolved hotin hexane/ ethyl acetate 4:1. On cooling slowly to approximately 30°there crystallise 1.82 g of racemic (2R*,2S*)-2-formamino-3-acetoxy-4-methyl-4-pentenoic acid ethyl ester having a melting point of 98°-106°. The mother liquor is slowly cooled to -12° C. and kept at that temperature for one hour.Filtration yields 15.04 g of acetate 3, m.p. 73°-75°, [α]D =-75.6° (c=1, CHCl3), analysis by gas chromatography (Chirasil®-L-Val, 160°-180°, 1° per minute): (2R,3S)-isomer 93.5% (Tret =14.5 minutes), (2S,3R)-isomer 2.2% (Tret =14.8 minutes), (2R,3R)-isomer 2.2% (Tret =16.8 minutes), (2S,3S)-isomer 2.1% (Tret =17.1 minutes). 20.64 g of anhydrous potassium carbonate are added at -16° to a solution of (2R,3S)-2-formylamino-3-acetoxy-4-methyl-4-pentenoic acid ethyl ester (3) in 400 ml of absolute ethanol. After stirring at -18° to -11° C. for 4 hours, 500 ml of buffer solution (1 molar, phosphate, pH=7) are added dropwise. The mixture is stirred at roomtemperature for 30 minutes and extracted three times with 350 ml of dichloromethane each time. The organic phases are dried over sodium sulphate and concentrated by evaporation, and the residue is chromatographed on 1 kg of silica gel using hexane/ethyl acetate 1:2 as eluant, yielding 9.8 g of alcohol 1.

Provenance & Evidence