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

HRID 1857589Notes

Reaction equation

HRID 1857589 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 48.4%

Reagents, catalysts & solvents 2

HCID 887MethanolSolventHCID 8028TetrahydrofuranSolvent

Procedure

To a solution of N-benzyloxycarbonyl-L-phenylalanine chloromethyl ketone (75 g, 0.2 mol) in a mixture of 800 mL of methanol and 800 mL of tetrahydrofuran was added sodium borohydride (13.17 g, 0.348 mol, 1.54 equiv.) over 100 min. The solution was stirred at room temperature for 2 h and then concentrated in vacuo. The residue was dissolved in 1000 mL of ethyl acetate and washed with 1N KHSO4, saturated aqueous NaHCO3, saturated aqueous NaCl, dried over anhyd MgSO4, filtered and concentrated in vacuo to give an oil. The crude product was dissolved in 1000 mL of hexanes at 60° C. and allowed to cool to room temperature whereupon crystals formed that were isolated by filtration and washed with copious amounts of hexanes. This solid was then recrystallized from hot ethyl acetate and hexanes to provide 32.3 g 43% of N-benzyloxycarbonyl-3(S)-amino-1-chloro-4-phenyl-2(S)-butanol, mp 150-151° C., FAB MS: MLi+ =340.

Workup

  1. concentrationconcentrated in vacuo
  2. dissolutionThe residue was dissolved in 1000 mL of ethyl acetate
  3. washwashed with 1N KHSO4, saturated aqueous NaHCO3, saturated aqueous NaCl
  4. dry with materialdried over anhyd MgSO4
  5. filtrationfiltered
  6. concentrationconcentrated in vacuo
  7. customto give an oil
  8. temperatureto cool to room temperature whereupon crystals
  9. customformed
  10. customthat were isolated by filtration
  11. washwashed with copious amounts of hexanes
  12. customThis solid was then recrystallized from hot ethyl acetate and hexanes

Sources & evidence

ORD record
ord-68352df2c85f440cbe652a3b426ae739
Source dataset
uspto-grants-2000_11
Patent number
US06147117

Reaction notes

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