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

HRID 1450667Notes

Reaction equation

HRID 1450667 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.[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 5360545SodiumHCID 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 borehydride 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. waitborehydride over one hundred minutes
  2. customThe solvents were removed under reduced pressure at 40° C.
  3. dissolutionthe residue dissolved in ethyl acetate (approx. 1L)
  4. washThe solution was washed sequentially with 1M potassium hydrogen sulfate, saturated sodium bicarbonate
  5. dry with materialAfter drying over anhydrous magnesium sulfate
  6. filtrationfiltering
  7. customthe solution was removed under reduced pressure
  8. additionTo the resulting oil was added hexane (approx. 1L)
  9. temperatureAfter cooling to room temperature
  10. customthe solids were collected
  11. washwashed with 2L of hexane
  12. customThe resulting solid was recrystallized from hot ethyl acetate and hexane

Sources & evidence

ORD record
ord-983bb7bd05f248e49a105484b23b07f4
Source dataset
uspto-grants-1997_02
Patent number
US05602175

Reaction notes

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