Acetic Acid → (6R, 7S)-2,2-dimethyl-7-(1-methoxy-1-methylethyl)-1-aza-3-oxabicyclo[4.2.0]octan-8-one

HRID 235753Notes

Reaction equation

HRID 235753 reaction equation
[H-].[Na+].[CH3:3][C:4]1([CH3:17])[O:11][CH2:10][CH2:9][C@H:8]2[N:5]1[C:6](=[O:16])[C@@H:7]2[C:12]([OH:15])([CH3:14])[CH3:13].S(OC)(O[CH3:22])(=O)=O.C(O)(=O)C>CN(C)C=O>[CH3:3][C:4]1([CH3:17])[O:11][CH2:10][CH2:9][C@H:8]2[N:5]1[C:6](=[O:16])[C@@H:7]2[C:12]([O:15][CH3:22])([CH3:13])[CH3:14]

Participants

6

Reactant 4

HCID 176Acetic AcidHCID 6497Dimethyl SulfateHCID 24758Sodium hydrideHCID 13194415(6R,7S)-2,2-dimethyl-7-(1-hydroxy-1-methylethyl)-1-aza-3-oxabicyclo[4,2,0]-octan-8-one

Product 1

HCID 56631074(6R, 7S)-2,2-dimethyl-7-(1-methoxy-1-methylethyl)-1-aza-3-oxabicyclo[4.2.0]octan-8-one

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent3×

Conditions

Temperature
0 °C

Procedure

To a suspension of sodium hydride (38.1 mg, 50% in mineral oil) in N,N-dimethylformamide (1.14 ml) was added dropwise a solution of (6R, 7S)-2,2-dimethyl-7-(1-hydroxy-1-methylethyl)-1-aza-3-oxabicyclo[4.2.0]-octan-8-one (84.6 mg) in N,N-dimethylformamide (25.4 ml) at 0° C. After stirring for 30 minutes at 0° C., thereto was added a solution of dimethyl sulfate (75.13 μl) in N,N-dimethylformamide (0.676 ml), and the resultant mixture was stirred for 3 hours at 0° C. and for additional 1.5 hours at ambient temperature. Acetic acid (0.046 ml) was added to the mixture, and the solvent was distilled off in vacuo. The residue was diluted with ethyl acetate (20 ml) and then washed with an aqueous sodium chloride, 10% aqueous sodium bicarbonate, and a saturated aqueous sodium chloride in turn. The aqueous washings were extracted with ethyl acetate, and this extract was washed with an aqueous sodium chloride. The combined extracts were dried over magnesium sulfate, filtered and evaporated in vacuo. The residue (92.9 mg) was chromatographed on silica gel (2.5 g) eluting with a mixture of ethyl acetate and methylene chloride (1:100 to 1:3) to give (6R, 7S)-2,2-dimethyl-7-(1-methoxy-1-methylethyl)-1-aza-3-oxabicyclo[4.2.0]-octan-8-one (69.1 mg) as a pale yellow solid.

Workup

  1. distillationthe solvent was distilled off in vacuo
  2. additionThe residue was diluted with ethyl acetate (20 ml)
  3. washwashed with an aqueous sodium chloride, 10% aqueous sodium bicarbonate
  4. extractionThe aqueous washings were extracted with ethyl acetate
  5. washthis extract was washed with an aqueous sodium chloride
  6. dry with materialThe combined extracts were dried over magnesium sulfate
  7. filtrationfiltered
  8. customevaporated in vacuo
  9. customThe residue (92.9 mg) was chromatographed on silica gel (2.5 g)
  10. washeluting with a mixture of ethyl acetate and methylene chloride (1:100 to 1:3)

Sources & evidence

ORD record
ord-3758c9f74a8042889a776e50350f198b
Source dataset
uspto-grants-1987_02
Patent number
US04640915

Reaction notes

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