反应详情

1-Chloroisobutyl propionate (0.20 mL) was added to a mixture of 4 Å molecular sieves (125 mg), tetra-n-hexylammonium iodide (40 mg, 0.083 mmol), and (2-(((4-(1,3-Dihydro-1-oxo-2H-isoindol-2-yl)butyl)hydroxyphosphinyl)methyl)-4-phenylbutanoyl)-L-leucine N-phenylamide (50 mg, 0.081 mmol).6The mixture was warmed in an oil bath at 65°-70° C. for 7 h, then allowed to stand at room temperature overnight. The mixture was diluted into ethyl acetate (25 mL) and washed with 2N aqueous hydrochloric acid (25 mL) and saturated aqueous sodium chloride, and the organic layer was dried (sodium sulfate), decanted, and evaporated. The crude product was purified by flash column chromatography on silica gel (3 g) eluting with 20% acetone/dichloromethane to give 19 mg.(32% yield) of (2-(((4-(1,3-dihydro-1-oxo-2H-isoindol-2-yl)butyl)(2-methyl-1-(1-oxopropoxy)propoxy)phosphinyl)methyl)-4-phenylbutanoyl)-L-leucine N-phenylamide.

1. temperaturewas warmed in an oil bath at 65°-70° C. for 7 h
2. washwashed with 2N aqueous hydrochloric acid (25 mL) and saturated aqueous sodium chloride
3. dry with materialthe organic layer was dried (sodium sulfate)
4. customdecanted
5. customevaporated
6. customThe crude product was purified by flash column chromatography on silica gel (3 g)
7. washeluting with 20% acetone/dichloromethane
8. customto give 19 mg