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

HRID 1838468Notes

Reaction equation

HRID 1838468 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 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. 1L). 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. 1L) and the mixture warmed to 60° C. with swirling. After cooling to room temperature, the solids were collected and washed with 2L 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.

Workup

  1. customThe solvents were removed under reduced pressure at 40° C.
  2. dissolutionthe residue dissolved in ethyl acetate (approx. 1L)
  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 To the resulting oil
  7. additionwas added hexane (approx. 1L)
  8. temperatureAfter cooling to room temperature
  9. customthe solids were collected
  10. washwashed with 2L of hexane
  11. customThe resulting solid was recrystallized from hot ethyl acetate and hexane

Sources & evidence

ORD record
ord-5c10722b1a2f4dfaa8d8bc87408b02d3
Source dataset
uspto-grants-2004_01
Patent number
US06673822B2

Reaction notes

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