Dimethylformamide → HCID 131711547, compound

HRID 971418Notes

Reaction equation

HRID 971418 reaction equation
[C:1]([CH:4]1[O:10][CH:9]2[C:6]([C:26](=[O:34])[CH2:27][C:28]3[CH:33]=[CH:32][CH:31]=[CH:30][CH:29]=3)([C:7](=[O:25])[N:8]2[C:11](=[C:22]([CH3:24])[CH3:23])[C:12]([O:14][CH2:15][C:16]2[CH:21]=[CH:20][CH:19]=[CH:18][CH:17]=2)=[O:13])[NH:5]1)([OH:3])=O.[CH3:35]N(C)C=O.C(Cl)(=O)C(Cl)=O>C1C=CC=CC=1>[C:1]([CH:4]1[O:10][CH:9]2[C:6]([C:26](=[O:34])[CH2:27][C:28]3[CH:33]=[CH:32][CH:31]=[CH:30][CH:29]=3)([C:7](=[O:25])[N:8]2[C:11](=[C:22]([CH3:24])[CH3:23])[C:12]([O:14][CH2:15][C:16]2[CH:21]=[CH:20][CH:19]=[CH:18][CH:17]=2)=[O:13])[NH:5]1)(=[O:3])[CH3:35]

Participants

5

Reactant 3

HCID 6228DimethylformamideHCID 65578Oxalyl chlorideHCID 131711535HCID 131711535, compound

Product 1

HCID 131711547HCID 131711547, compoundYield 79.7%

Reagents, catalysts & solvents 1

HCID 241BenzeneSolvent

Procedure

To a solution of 10 g of benzyl α-(3ξ-carboxy-2-phenylacetyl-7-oxo-4-oxa-2,6-diazabicyclo[3.2.0]heptan-6-yl)-α-isopropylideneacetate in 120 ml of benzene are added 0.25 ml of N,N-dimethylformamide and 2.2 ml of oxalyl chloride, and the mixture stirred at room temperature for 45 minutes. The resulting solution of benzyl α-(3ξ-chlorocarbonyl-2-phenylacetyl-7-oxo-4-oxa-2,6-diazabicyclo[3.2.0]heptan-6-yl)-α-isopropylideneacetate is concentrated to about 1/2 volume, then dropwise added to a solution of diazomethane in 250 ml of ether (which has been prepared from 13 g of nitrosomethyl-urea) under ice-cooling, and stirred for 20 minutes. The resulting solution of benzyl α-(3ξ-diazoacetyl-2-phenylacetyl-7-oxo-4-oxa-2,6-diazabicyclo[3.2.0]heptan-6-yl)-α-isopropylideneacetate is mixed with 10 ml of ether containing 16% hydrogen chloride, and after 85 minutes, the mixture is concentrated under reduced pressure. The residue [benzyl α-(3ξ-chloroacetyl-2-phenylacetyl-7-oxo-4 -oxa-2,6-diazabicyclo[3.2.0]heptan-6-yl)-α-isopropylideneacetate (IR: γmaxCHCl3 1786, 1724, 1674 cm-1)], is dissolved in 100 ml of acetic acid and mixed with 10 g of zinc powder which has preliminarily been washed with hydrochloric acid, water, ethanol and ether, and stirred at room temperature for 1.5 hours. The reaction mixture is filtrated, and the filtrate poured into 90 ml of ice water and extracted with methylene chloride. The extract is washed with water, an aqueous solution of sodium hydrogencarbonate and then water, dried on sodium sulfate and concentrated under reduced pressure. The residue (9.68 g) is purified by chromatography on 200 g of silica gel containing 10% water and eluted with a mixture of benzene and ethyl acetate (7:1) to yield 7.208 g of benzyl α-(3ξ-acetyl-2-phenylacetyl-7-oxo-4-oxa-2,6-diazabicyclo[3.2.0]heptan-6-yl)-α-isopropylideneacetate in 79.7% yield.

Workup

  1. concentrationThe resulting solution of benzyl α-(3ξ-chlorocarbonyl-2-phenylacetyl-7-oxo-4-oxa-2,6-diazabicyclo[3.2.0]heptan-6-yl)-α-isopropylideneacetate is concentrated to about 1/2 volume
  2. additiondropwise added to a solution of diazomethane in 250 ml of ether (which has been prepared from 13 g of nitrosomethyl-urea) under ice-
  3. temperaturecooling
  4. stirringstirred for 20 minutes
  5. additionThe resulting solution of benzyl α-(3ξ-diazoacetyl-2-phenylacetyl-7-oxo-4-oxa-2,6-diazabicyclo[3.2.0]heptan-6-yl)-α-isopropylideneacetate is mixed with 10 ml of ether containing 16% hydrogen chloride
  6. waitafter 85 minutes
  7. concentrationthe mixture is concentrated under reduced pressure
  8. dissolutionThe residue [benzyl α-(3ξ-chloroacetyl-2-phenylacetyl-7-oxo-4 -oxa-2,6-diazabicyclo[3.2.0]heptan-6-yl)-α-isopropylideneacetate (IR: γmaxCHCl3 1786, 1724, 1674 cm-1)], is dissolved in 100 ml of acetic acid
  9. additionmixed with 10 g of zinc powder which
  10. washhas preliminarily been washed with hydrochloric acid, water, ethanol and ether
  11. stirringstirred at room temperature for 1.5 hours
  12. filtrationThe reaction mixture is filtrated
  13. additionthe filtrate poured into 90 ml of ice water
  14. extractionextracted with methylene chloride
  15. washThe extract is washed with water
  16. dry with materialan aqueous solution of sodium hydrogencarbonate and then water, dried on sodium sulfate
  17. concentrationconcentrated under reduced pressure
  18. customThe residue (9.68 g) is purified by chromatography on 200 g of silica gel containing 10% water
  19. washeluted with a mixture of benzene and ethyl acetate (7:1)

Sources & evidence

ORD record
ord-f817a8af6aa74623bde7df39376e7cc3
Source dataset
uspto-grants-1979_07
Patent number
US04159984

Reaction notes

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