Sodium borohydride → Benzyl ((2S,3S)-4-chloro-3-hydroxy-1-phenylbutan-2-yl)carbamate

HRID 53660Notes

Reaction equation

HRID 53660 reaction equation
[Cl:1][CH2:2]C(CCl)=O.[CH2:7]([O:14][C:15]([NH:17][C@H:18]([C:26]([OH:28])=O)[CH2:19][C:20]1[CH:25]=[CH:24][CH:23]=[CH:22][CH:21]=1)=[O:16])[C:8]1[CH:13]=[CH:12][CH:11]=[CH:10][CH:9]=1.[BH4-].[Na+]>CO.O1CCCC1>[CH2:7]([O:14][C:15]([NH:17][C@@H:18]([CH2:19][C:20]1[CH:21]=[CH:22][CH:23]=[CH:24][CH:25]=1)[C@H:26]([OH:28])[CH2:2][Cl:1])=[O:16])[C:8]1[CH:9]=[CH:10][CH:11]=[CH:12][CH:13]=1

Participants

5

Reactant 2

HCID 4311764Sodium borohydrideHCID 21117419N-benzyloxycarbonyl-L-phenylalanine chloromethyl ketone

Product 1

HCID 10860587Benzyl ((2S,3S)-4-chloro-3-hydroxy-1-phenylbutan-2-yl)carbamateYield 43%

Reagents, catalysts & solvents 2

HCID 887MethanolSolventHCID 8028TetrahydrofuranSolvent

Conditions

Temperature
60 °C

Procedure

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.

Workup

  1. customThe solvents were removed under reduced pressure at 40° C.
  2. dissolutionthe residue dissolved in ethyl acetate (approx. 1 L)
  3. washThe solution was washed sequentially with 1M potassium hydrogen sulfate, saturated sodium bicarbonate
  4. dry with materialAfter drying over anhydrous magnesium sulfate
  5. filtrationfiltering
  6. customthe solution was removed under reduced pressure
  7. additionTo the resulting oil was added hexane (approx. 1 L)
  8. temperatureAfter cooling to room temperature
  9. customthe solids were collected
  10. washwashed with 2 L of hexane
  11. customThe resulting solid was recrystallized from hot ethyl acetate and hexane

Sources & evidence

ORD record
ord-a03cd79ccf684ed88f0693e8ca6e88c1
Source dataset
uspto-grants-1997_04
Patent number
US05620977

Reaction notes

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