Hydrochloric Acid → 4-benzyl-3-[(E) 6-(1,3-dihydro-4-hydroxy-6-methoxy-7-methyl-3-oxoisobenzofuran-5-yl)-2,4-dimethyl-4-hexenoyl]-2-oxazolidinone

Participants

Reaction Conditions

Reaction Steps

A 1M solution of sodium bis(trimethylsilyl)amide in tetrahydrofuran (0.43L, 0.43 mol) was cooled to -78° C. and treated dropwise with a precooled solution of (S) 4-benzyl-3-[(E) 6-(1,3-dihydro-4-hydroxy -6-methoxy-7-methyl-3-oxoisobenzofuran-5-yl)-4-methyl-4-hexenoyl]-2-oxazolidinone (86 g, 0.179 mol) in tetrahydrofuran (250 mL), maintaining a temperature below -65° C. After 15 minutes stirring, iodomethane (56 mL, 0.9 mol) was added and the solution was warmed to -30° C. After 1 hour, the solution was warmed to 0° C. and 2N hydrochloric acid (0.4L) was added. The organic layer was washed with 2% sodium sulfite (0.2L) and brine (0.2L) and dried over sodium sulfate. After filtration, the volatiles were distilled at reduced pressure and the residue was applied to a bed of silica gel (0.45 kg). Elution with 40% ethyl acetate/hexane (4L) and concentration of the eluent gave the alkylation product (S) 4-benzyl-3-[(E) 6-(1,3-dihydro-4-hydroxy-6-methoxy-7-methyl-3-oxoisobenzofuran-5-yl) -2,4-dimethyl-4-hexenoyl]-2-oxazolidinone as a white foam. The product consisted of an 85:13 mixture of diastereomers at the 2-hexenoyl position.

Provenance & Evidence