Réaction #640535

Équation de réaction

N-benzyloxycarbonyl-L-phenylalanine chloromethyl ketone

sodium borohydride

→

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

Rendement 43.0%

Solvants

methanol

tetrahydrofuran

Conditions de réaction

Traitement

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

Mode opératoire

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 solutions. 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+=340.

Source