Reacción #81938

Ecuación de reacción

N-benzyloxycarbonyl-L-phenylalanine chloromethyl ketone

sodium borohydride

→

N-benzyloxycarbonyl-3(S)-amino-1-chloro-4-phenyl-2(S)-butanol

Rendimiento 43.0%

Disolventes

methanol

tetrahydrofuran

Condiciones de reacción

Tratamiento posterior

1. 1
   OtroThe solvents were removed under reduced pressure at 40° C.
2. 2
   workup.DISSOLUTIONthe residue dissolved in ethyl acetate (approx. 1 L)
3. 3
   LavadoThe solution was washed sequentially with 1M potassium hydrogen sulfate, saturated sodium bicarbonate
4. 4
   SecadoAfter drying over anhydrous magnesium sulfate
5. 5
   Filtraciónfiltering
6. 6
   Otrothe solution was removed under reduced pressure
7. 7
   workup.ADDITIONTo the resulting oil was added hexane (approx. 1 L)
8. 8
   TemperaturaAfter cooling to room temperature
9. 9
   Otrothe solids were collected
10. 10
    Lavadowashed with 2 L of hexane
11. 11
    OtroThe resulting solid was recrystallized from hot ethyl acetate and hexane

Procedimiento

Part A. To a solution of 75.0 g (0.226 mol) of N-benzyloxycarbonyl-L-phenylalanine chloromethyl ketone in a mixture of 807 mL of methanol and 807 mL of tetrahydrofuran at -2° C., was added 13.17 g (0.348 mol, 1.54 equiv.) of solid sodium borohydride over one hundred minutes. The solvents were removed under reduced pressure at 40° C. and the residue dissolved in ethyl acetate (approx. 1 L). The solution was washed sequentially with 1M potassium hydrogen sulfate, saturated sodium bicarbonate and then saturated sodium chloride solution. After drying over anhydrous magnesium sulfate and filtering, the solution was removed under reduced pressure. To the resulting oil was added hexane (approx. 1 L) and the mixture warmed to 60° C. with swirling. After cooling to room temperature, the solids were collected and washed with 2 L of hexane. The resulting solid was recrystallized from hot ethyl acetate and hexane to afford 32.3 g (43% yield) of N-benzyloxycarbonyl-3(S)-amino-1-chloro-4-phenyl-2(S)-butanol, mp 150°-151° C. and M+Li+ 32 340.

Fuente