Hydrochloric Acid → Tert-butyl ((2S,3S)-1-(benzyloxy)-2-(hydroxymethyl)-4-oxoazetidin-3-yl)carbamate

HRID 414859Notes

Reaction equation

HRID 414859 reaction equation
[BH4-].[Na+].Cl.S([O-])(O)(=O)=O.[K+].[CH2:10]([O:17][N:18]1[C@H:21]([C:22](OC)=[O:23])[C@H:20]([NH:26][C:27]([O:29][C:30]([CH3:33])([CH3:32])[CH3:31])=[O:28])[C:19]1=[O:34])[C:11]1[CH:16]=[CH:15][CH:14]=[CH:13][CH:12]=1>O1CCCC1.O>[CH2:10]([O:17][N:18]1[C@H:21]([CH2:22][OH:23])[C@H:20]([NH:26][C:27]([O:29][C:30]([CH3:32])([CH3:31])[CH3:33])=[O:28])[C:19]1=[O:34])[C:11]1[CH:16]=[CH:15][CH:14]=[CH:13][CH:12]=1

Participants

7

Reactant 4

HCID 313Hydrochloric AcidHCID 516920Potassium bisulfateHCID 4311764Sodium borohydrideHCID 22840984(3S,4S)-1-benzyloxy-3-(tert-butoxycarbonylamino)-4-methoxycarbonyl-2-azetidinone

Product 1

HCID 13488997Tert-butyl ((2S,3S)-1-(benzyloxy)-2-(hydroxymethyl)-4-oxoazetidin-3-yl)carbamateYield 11.4%

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 8028TetrahydrofuranSolvent

Procedure

In 20 ml of tetrahydrofuran is dissolved 1.9 g [5.4 mmole) of (3S,4S)-1-benzyloxy-3-(tert-butoxycarbonylamino)-4-methoxycarbonyl -2-azetidinone obtained in the same manner as the method described in The Journll of Organic Chemistry, 48(1983), 3556-3559, and a solution of 410 mg (10.8 mmole) of sodium borohydride in 4 ml of water is added dropwise to the solution over the 10-minute period. After the addition is completed, the reaction solution is stirred under ice-cooling for 20 minutes, and 3 ml of 3N hydrochloric acid is added to stop the reaction. 10 ml of 0.6M aqueous potassium hydrogen sulfate solution is added, followed by extraction with ethyl acetate. The extract is washed with saturated aqueous sodium hydrogen carbonate solution and aqueous sodium chloride solution successively, and dried over anhydrous magnesium sulfate. The solvent is distilled off under reduced pressure, and the residue is purified by column chromatography (silica gel, 100 g;h-hexane-ethyl acetate, 2:1, then 1:1). The fractions containing the objective compound are collected the solvent is distilled off under reduced pressure, and after ether and n-hexane are added to the residue, the resulting crystals are recovered by filtration to give 200 mg (11.4%) of (3S,4S)-1-benzyloxy-3-(tert-butoxycarbonylamino)-4-hydroxymethyl-2-azetidinone.

Workup

  1. customobtained in the same manner as the method
  2. additionAfter the addition
  3. temperaturecooling for 20 minutes
  4. customthe reaction
  5. extractionfollowed by extraction with ethyl acetate
  6. washThe extract is washed with saturated aqueous sodium hydrogen carbonate solution and aqueous sodium chloride solution successively
  7. dry with materialdried over anhydrous magnesium sulfate
  8. distillationThe solvent is distilled off under reduced pressure
  9. customthe residue is purified by column chromatography (silica gel, 100 g
  10. additionThe fractions containing the objective compound
  11. customare collected the solvent
  12. distillationis distilled off under reduced pressure
  13. additionafter ether and n-hexane are added to the residue
  14. filtrationthe resulting crystals are recovered by filtration

Sources & evidence

ORD record
ord-9fa9e3c7a1b94415a8b16f1131f2a618
Source dataset
uspto-grants-1988_12
Patent number
US04794108

Reaction notes

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