Reaction #640535

Reaction equation

N-benzyloxycarbonyl-L-phenylalanine chloromethyl ketone

sodium borohydride

→

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

Yield 43.0%

Solvents

methanol

tetrahydrofuran

Conditions

Workup

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

Procedure

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