Reaktion #214979

Reaktionsgleichung

hydrochloric acid

AT-125

sodium bicarbonate

9-hydroxymethyl fluorenylcarbonyl chloride

→

3-chloro-α-[[(9H-fluoren-9-yl-methoxy)carbonyl]amino]-4,5-dihydro-5-isoxazole acetic acid

Lösungsmittel

water

ethyl acetate

Reaktionsbedingungen

Aufarbeitung

1. 1
   TemperaturAfter cooling the mixture to 0°-5° C.
2. 2
   workup.WAITto stand overnight at room temperature
3. 3
   SonstigeThe organic phase is separated
4. 4
   Trocknendried over sodium sulfate
5. 5
   Einengenconcentrated
6. 6
   Sonstigechromatographed on 20 g
7. 7
   workup.ADDITIONThose fractions containing the desired product
8. 8
   Sonstigeare evaporated
9. 9
   Sonstigethe residue recrystallized from ethyl acetate

Vorschrift

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 1 N 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.

Quelle