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

HRID 2087028Notes

Reaction equation

HRID 2087028 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

To a solution of 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., is added 1.54 equiv. of solid sodium borohydride over one hundred minutes. The solvents are then removed under reduced pressure at 40° C. and the residue is dissolved in ethyl acetate (approx. 1L). The solution is washed sequentially with 1M potassium hydrogen sulfate, saturated sodium bicarbonate and is then saturated sodium chloride solutions. After drying over anhydrous magnesium sulfate and filtering, the solution is removed under reduced pressure. To the resulting oil is added hexane (approx. 1L) and the mixture is warmed to 60° C. with swirling. After cooling to room temperature, the solids are collected and washed with 2L of hexane. The resulting solid is 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.

Workup

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

Sources & evidence

ORD record
ord-24c210dce0a54f9ea9a4a0634624e181
Source dataset
uspto-grants-2004_04
Patent number
US06727282B2

Reaction notes

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