Trimethyl orthoacetate → (S)-6-(2-Methyl-allyl)-3-{(S)-1-[4-(5-methyl-[1,3,4]oxadiazol-2-yl)-phenyl]-ethyl}-6-phenyl-[1,3]oxazinan-2-one

Participants

Reaction Conditions

Reaction Steps

A mixture of 4-{(S)-1-[(S)-6-(2-hydroxy-2-methyl-propyl)-2-oxo-6-phenyl-[1,3]oxazinan-3-yl]-ethyl}-benzoic acid hydrazide (90 mg), toluene-4-sulfonic acid monohydrate (10 mg), and 1,1,1-trimethoxy-ethane (1 ml) was stirred at room temperature for 1 h, at 80° C. for 2 h, and finally at reflux temperature for 1.5 h. After cooling to ambient temperature, ethyl acetate was added and the resulting mixture was washed with aqueous NaHCO3 solution and brine. The solvent was removed under reduced pressure and the residue was purified by chromatography on silica gel (CH2Cl2/MeOH 99:1->95:5) to afford the title compound in a mixture with the double bond isomer (S)-6-(2-methyl-allyl)-3-{(S)-1-[4-(5-methyl-[1,3,4]oxadiazol-2-yl)-phenyl]-ethyl}-6-phenyl-[1,3]oxazinan-2-one (ca. 64:36) as a colorless resin-like solid.

Provenance & Evidence