反应详情

To a solution of ethyl 1-methyl-1-(4-bromomethylphenyl)ethanesulfonate (0.64 g, 1.89 mol) and N-diphenylmethyleneglycine t butyl ester (0.586 g, 1.98 mmol) in THF (6.5 mL) cooled on ice was added sodium bis(trimethylsilyl)amide (2M in THF, 1.04 mL). After 30 minutes the solvent was evaporated, the residue was taken up in acetic acid (2 mL), water (2 mL) and methanol (4 mL), and stirred at rt for 4 hours. The methanol was evaporated, water was added, and the mixture was washed with hexane/ether 1/1 (2×20 mL). The organic phase was washed with water. The combined aqueous phase was cooled on ice, and adjusted to pH 7 with sodium bicarbonate. Dioxane was added followed by benzyl chloroformate (0.38 mL, 2.65 mmol) and the mixture was stirred coming to rt overnight. Water was added, and the mixture was acidified to pH 3 with 1N H2SO4. The mixture was extracted with ethyl acetate, and the organic phase was dried, filtered and evaporated. Chromatography of the residue over silica gel (10% to 20% ethyl acetate/hexane) gave crude 2-(R,S)-benzyloxycarbonylamino-3-[4'-(1"-ethyloxysulfonyl-1"-methyl)ethyl)benzene]propanoic acid t butyl ester (0.645 g, 68%). To a solution of the crude ester in methylene chloride (9 mL) cooled on ice was added trifluoroacetic acid (1.5 mL). The mixture was stirred for 4 hours, warming to rt. The reaction was quenched with cold aqueous sodium bicarbonate, and extracted with methylene chloride. The solvent was evaporated, and chromatography of the residue over silica gel (methylene chloride to 10% methanol/methylene chloride) gave 2-(R,S)-benzyloxycarbonylamino-3-[4'-(1"-ethyloxysulfonyl-1"-methyl)ethyl)benzene]propanoic acid (0.396 g, 0.88 mmol, 69%).

1. customAfter 30 minutes the solvent was evaporated
2. customThe methanol was evaporated
3. additionwater was added
4. washthe mixture was washed with hexane/ether 1/1 (2×20 mL)
5. washThe organic phase was washed with water
6. temperatureThe combined aqueous phase was cooled on ice
7. additionDioxane was added
8. stirringthe mixture was stirred
9. waitcoming to rt overnight
10. extractionThe mixture was extracted with ethyl acetate
11. customthe organic phase was dried
12. filtrationfiltered
13. customevaporated