反应详情

A mixture of sodium carbonate (10.20 g, 96.2 mmol) in water (170 ml) is added to a mixture of (R)-2-(methoxycarbonylamino)-3-phenylpropanoic acid (II, EXAMPLE 1, ˜0.148 mol crude) in methylene chloride. Methoxylamine hydrochloride (14.2 g, 0.170 mol) and 1-(3-dimethylaminopropyl)-3-ethylcarbodiimide hydrochloride (EDC) (31.21 g, 0.163 mol) are added, and the mixture is stirred at 20-25° for 22 hours. The mixture is diluted with tetrahydrofuran (to dissolve the precipitate) and the layers are separated. The aqueous layer is extracted with 1:1 tetrahydrofuran/ether, and the combined organic extracts are washed with hydrochloric acid (10%) and saturated sodium bicarbonate solution. The mixture is dried over magnesium sulfate, filtered and the solvent removed under reduced pressure. Crystallization from ethyl acetate gives the title compound, mp=154-155°; NMR (CDCl3) 3.05, 3.58, 3.61, 4.34, 5.66, 7.15-7.31 and 9.44 δ; IR (mineral oil) 1694 and 1668 cm−1; [a]25D=+5.2° (CH3OH, c=1.045).

1. dissolutionto dissolve the precipitate) and the layers
2. customare separated
3. extractionThe aqueous layer is extracted with 1:1 tetrahydrofuran/ether
4. washthe combined organic extracts are washed with hydrochloric acid (10%) and saturated sodium bicarbonate solution
5. dry with materialThe mixture is dried over magnesium sulfate
6. filtrationfiltered
7. customthe solvent removed under reduced pressure
8. customCrystallization from ethyl acetate