Sodium hydride → HCID 69796701, compound

HRID 984429Notes

Reaction equation

HRID 984429 reaction equation
[CH3:1][CH:2]([C:13]([CH3:15])=[O:14])[C:3]([O:5][CH2:6][C:7]1[CH:12]=[CH:11][CH:10]=[CH:9][CH:8]=1)=[O:4].[H-].[Na+].[Si:18]([O:25][C@@H:26]([C@@H:28]1[C@@H:31](SC2C=CC=CC=2)[NH:30][C:29]1=[O:39])[CH3:27])([C:21]([CH3:24])([CH3:23])[CH3:22])([CH3:20])[CH3:19].[Cl-].[NH4+]>O1CCCC1>[Si:18]([O:25][C@@H:26]([C@@H:28]1[C@@H:31]([C:2]([C:13](=[O:14])[CH3:15])([C:3]([O:5][CH2:6][C:7]2[CH:12]=[CH:11][CH:10]=[CH:9][CH:8]=2)=[O:4])[CH3:1])[NH:30][C:29]1=[O:39])[CH3:27])([C:21]([CH3:22])([CH3:23])[CH3:24])([CH3:19])[CH3:20]

Participants

6

Reactant 4

HCID 24758Sodium hydrideHCID 25517Ammonium ChlorideHCID 440192Benzyl 2-methyl-3-oxobutanoateHCID 11089029HCID 11089029, compound

Product 1

HCID 69796701HCID 69796701, compoundYield 77.6%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

Benzyl 2-methylacetoacetate (825 mg, 4.00 mmole) was added to a suspension of sodium hydride (160 mg, 4.0 mmole) in tetrahydrofuran (10 ml) in a nitrogen stream, and the solution mixture was stirred for 10 min at room temperature and then admixed with cuprous bromide dimethylsulfide complex (822 mg, 5.98 mmole), followed by stirring for 1 hour, addition of (3S,4R)-3-[(R)-1-(tert-butyldimethylsilyloxy)ethyl]-4-phenylthio-2-azetidinone (677 mg, 2.00 mmole) and stirring for 3 hours. The reaction solution was admixed with saturated ammonium chloride solution, and after the insoluble matters were removed by filtration, the filtrate was extracted with ethyl acetate. The ethyl acetate layer was washed with aqueous saturated sodium chloride solution three times, dried over magnesium sulfate and concentrated under reduced pressure, and the residue was purified by silica gel column chromatography (the developing solvent was a 3:1 mixture of n-hexane and ethyl acetate) to give 673 mg (77.6%) of the subject compound consisting of a diastereomer mixture (Products A and B) at a ratio of about 1:1 in the form of colorless oily matter.

Workup

  1. stirringby stirring for 1 hour
  2. stirringstirring for 3 hours
  3. customafter the insoluble matters were removed by filtration
  4. extractionthe filtrate was extracted with ethyl acetate
  5. washThe ethyl acetate layer was washed with aqueous saturated sodium chloride solution three times
  6. dry with materialdried over magnesium sulfate
  7. concentrationconcentrated under reduced pressure
  8. customthe residue was purified by silica gel column chromatography (the developing solvent
  9. additiona 3:1 mixture of n-hexane and ethyl acetate)

Sources & evidence

ORD record
ord-089d43a2917a4dd2801a0ca57c36a377
Source dataset
uspto-grants-2005_03
Patent number
US06867297B1

Reaction notes

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