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

HRID 971415Notes

Reaction equation

HRID 971415 reaction equation
C(C1OC2C(C(=O)CC3C=CC=CC=3)(C(=O)N2C(=C(C)C)C(OC)=O)N1)(O)=O.S(Cl)(Cl)=O.[N+](=[CH:35][C:36]([CH:38]1[O:44][CH:43]2[C:40]([C:54](=[O:62])[CH2:55][C:56]3[CH:61]=[CH:60][CH:59]=[CH:58][CH:57]=3)([C:41](=[O:53])[N:42]2[C:45](=[C:50]([CH3:52])[CH3:51])[C:46]([O:48][CH3:49])=[O:47])[NH:39]1)=[O:37])=[N-].[ClH:63]>C(Cl)Cl>[Cl:63][CH2:35][C:36]([CH:38]1[O:44][CH:43]2[C:40]([C:54](=[O:62])[CH2:55][C:56]3[CH:61]=[CH:60][CH:59]=[CH:58][CH:57]=3)([C:41](=[O:53])[N:42]2[C:45](=[C:50]([CH3:52])[CH3:51])[C:46]([O:48][CH3:49])=[O:47])[NH:39]1)=[O:37]

Participants

6

Reactant 4

HCID 313Hydrochloric AcidHCID 24386Thionyl ChlorideHCID 131711536Methyl alpha-(3xi-carboxy-2-phenylacetyl-7-oxo-4-oxa-2,6-diazabicyclo[3.2.0]heptan-6-yl)-alpha-isopropylideneacetateHCID 131711541Methyl alpha-(3xi-diazoacetyl-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]heptan-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-32f2da23196f49afbeb3c76f49ac9f50
Source dataset
uspto-grants-1979_07
Patent number
US04159984

Reaction notes

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