Hydrochloric Acid → Methyl alpha-(3xi-chloroacetyl-2-phenylacetyl-7-oxo-4-oxa-2,6-diazabicyclo[3.2.0]heptan-6-yl)-alpha-isopropylideneacetate

HRID 2287187Notes

Reaction equation

HRID 2287187 reaction equation
[C:1]([CH:4]1[O:10][CH:9]2[C:6]([C:20](=[O:28])[CH2:21][C:22]3[CH:27]=[CH:26][CH:25]=[CH:24][CH:23]=3)([C:7](=[O:19])[N:8]2[C:11](=[C:16]([CH3:18])[CH3:17])[C:12]([O:14][CH3:15])=[O:13])[NH:5]1)([OH:3])=O.S(Cl)(Cl)=O.[C:33](=CC([O-])=O)(C)C.[ClH:40]>C(Cl)Cl>[Cl:40][CH2:33][C:1]([CH:4]1[O:10][CH:9]2[C:6]([C:20](=[O:28])[CH2:21][C:22]3[CH:23]=[CH:24][CH:25]=[CH:26][CH:27]=3)([C:7](=[O:19])[N:8]2[C:11](=[C:16]([CH3:18])[CH3:17])[C:12]([O:14][CH3:15])=[O:13])[NH:5]1)=[O:3]

Participants

6

Reactant 4

HCID 313Hydrochloric AcidHCID 24386Thionyl ChlorideHCID 50813273-Methylbut-2-enoateHCID 131711536Methyl alpha-(3xi-carboxy-2-phenylacetyl-7-oxo-4-oxa-2,6-diazabicyclo[3.2.0]heptan-6-yl)-alpha-isopropylideneacetate

Product 1

HCID 131711540Methyl alpha-(3xi-chloroacetyl-2-phenylacetyl-7-oxo-4-oxa-2,6-diazabicyclo[3.2.0]heptan-6-yl)-alpha-isopropylideneacetateYield 75.3%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

To a solution of 1.45 g of methyl α-(3ξ-carboxy-2-phenylacetyl-7-oxo-4-oxa-2,6-diazabicyclo[3.2.0]heptan-6-yl)-α-isopropylideneacetate in 7 ml of methylene chloride is added 1.2 ml of thionyl chloride, and the mixture refluxed under heating for 2 hours and concentrated under reduced pressure. The resulting residue [methyl α-(3ξ-chlorocarbonyl-2-phenylacetyl-7-oxo-4-oxa-2,6-diazabicyclo[3.2.0]heptan-6-yl)-α-isopropylideneacetate] is dissolved in 20 ml of tetrahydrofuran and mixed with 15 ml of ether solution of diazomethane which has been prepared from 1.5 g of nitrosomethylurea, and the mixture is kept at room temperature for 30 minutes. Into the resulting solution of methyl α-(3ξ-diazoacetyl-2-phenylacetyl-7-oxo-4-oxa-2,6-diazabicyclo[3.2.0]heptn-6-yl)-α-isopropylideneacetate is introduced hydrogen chloride gas under ice-cooling until the spot of diazo ketone disappears. The mixture is concentrated under reduced pressure, and the residue is purified by chromatography on 17 g of silica gel containing 10% water and eluted with benzene containing 10% ethyl acetate to yield 1.19 g of methyl α-(3ξ-chloroacetyl-2-phenylacetyl-7-oxo-4-oxa-2,6-diazabicyclo[3.2.0]heptan-6-yl)-α-isopropylideneacetate in 75.3% yield.

Workup

  1. temperaturethe mixture refluxed
  2. temperatureunder heating for 2 hours
  3. concentrationconcentrated under reduced pressure
  4. dissolutionThe resulting residue [methyl α-(3ξ-chlorocarbonyl-2-phenylacetyl-7-oxo-4-oxa-2,6-diazabicyclo[3.2.0]heptan-6-yl)-α-isopropylideneacetate] is dissolved in 20 ml of tetrahydrofuran
  5. additionmixed with 15 ml of ether solution of diazomethane which
  6. customhas been prepared from 1.5 g of nitrosomethylurea
  7. concentrationThe mixture is concentrated under reduced pressure
  8. customthe residue is purified by chromatography on 17 g of silica gel containing 10% water
  9. washeluted with benzene containing 10% ethyl acetate

Sources & evidence

ORD record
ord-c72090ab479840ee999f68985a51346c
Source dataset
uspto-grants-1981_05
Patent number
US04269773

Reaction notes

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