反应详情

To 178 mg. of AT-125 in 4 ml. of water is added 300 mg. of sodium bicarbonate. After cooling the mixture to 0°-5° C., 300 mg. of 9-hydroxymethyl fluorenylcarbonyl chloride is added and it is stirred for two hours and allowed to stand overnight at room temperature. The resulting semi solid is taken up in ethyl acetate and 1N hydrochloric acid is added until a pH of 3 is attained. The organic phase is separated, dried over sodium sulfate, concentrated and chromatographed on 20 g. of CC-4 silica gel employing 40% ethyl acetate/Hexane. Those fractions containing the desired product are evaporated and the residue recrystallized from ethyl acetate to yield 3-chloro-α-[[(9H-fluoren-9-yl-methoxy)carbonyl]amino]-4,5-dihydro-5-isoxazole acetic acid, m.p. 182°-183° C. The NMR fits the desired structure.

1. temperatureAfter cooling the mixture to 0°-5° C.
2. waitto stand overnight at room temperature
3. customThe organic phase is separated
4. dry with materialdried over sodium sulfate
5. concentrationconcentrated
6. customchromatographed on 20 g
7. additionThose fractions containing the desired product
8. customare evaporated
9. customthe residue recrystallized from ethyl acetate