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

HRID 235756Notes

Reaction equation

HRID 235756 reaction equation
[CH3:1][C:2]1([CH3:15])[O:9][CH2:8][CH2:7][C@H:6]2[N:3]1[C:4](=[O:14])[C@H:5]2[C:10]([OH:13])([CH3:12])[CH3:11].[CH2:16]([Li])CCC.CN(C)P(=O)(N(C)C)N(C)C.COS(OC)(=O)=O>O1CCCC1.C(O)(=O)C>[CH3:1][C:2]1([CH3:15])[O:9][CH2:8][CH2:7][C@H:6]2[N:3]1[C:4](=[O:14])[C@H:5]2[C:10]([O:13][CH3:16])([CH3:11])[CH3:12]

Participants

7

Reactant 4

HCID 6497Dimethyl SulfateHCID 12679HexamethylphosphoramideHCID 13194414HCID 13194414, compoundHCID 178418339Butyllithium

Product 1

HCID 86741283(6R, 7R)-2,2-dimethyl-7-(1-methoxy-1-methylethyl)-1-aza-3-oxabicyclo[4.2.0]octan-8-one

Reagents, catalysts & solvents 2

HCID 176Acetic AcidSolventHCID 8028TetrahydrofuranSolvent2×

Procedure

To a solution of (6R, 7R)-2,2-dimethyl-7-(1-hydroxy-1-methylethyl)-1-aza-3-oxabicyclo[4.2.0]octan-8-one (43.0 mg) in tetrahydrofuran (1.29 ml) was added dropwise a solution of n-butyl lithium (0.128 ml of 1.74M solution in hexane) at -78° C. After stirring for 10 minutes at the same temperature, hexamethylphosphoric triamide (38.6 μl) was added to the mixture. The resultant solution was stirred for 10 minutes at -78° C. and a solution of dimethylsulfate (38.2 μl) in tetrahydrofuran (0.344 ml) was added to the mixture. The resultant mixture was allowed to warm to ambient temperature over a period of an hour and stirred at ambient temperature overnight. After acetic acid (12.7 μl) was added, the solvent was distilled off, and the residue was dissolved in ethyl acetate (10 ml) and washed with a mixture of 10% aqueous solution of sodium bicarbonate (0.3 ml) and a saturated aqueous sodium chloride (3 ml). The aqueous washings were extracted with ethyl acetate (10 ml) and the combined ethyl acetate extracts were washed with a saturated aqueous sodium chloride. After drying over magnesium sulfate, the ethyl acetate solution was filtered and evaporated in vacuo. The residue was chromatographed on silica gel (2.2 g) eluting with a mixture of ethyl acetate and methylene chloride (1:100 to 1:1) to give (6R, 7R)-2,2-dimethyl-7-(1-methoxy-1-methylethyl)-1-aza-3-oxabicyclo[4.2.0]octan-8-one (24.0 mg) as a white solid.

Workup

  1. additionwas added to the mixture
  2. distillationthe solvent was distilled off
  3. dissolutionthe residue was dissolved in ethyl acetate (10 ml)
  4. washwashed with a mixture of 10% aqueous solution of sodium bicarbonate (0.3 ml)
  5. extractionThe aqueous washings were extracted with ethyl acetate (10 ml)
  6. washthe combined ethyl acetate extracts were washed with a saturated aqueous sodium chloride
  7. dry with materialAfter drying over magnesium sulfate
  8. filtrationthe ethyl acetate solution was filtered
  9. customevaporated in vacuo
  10. customThe residue was chromatographed on silica gel (2.2 g)
  11. washeluting with a mixture of ethyl acetate and methylene chloride (1:100 to 1:1)

Sources & evidence

ORD record
ord-318f56705b764e539010787323090b3f
Source dataset
uspto-grants-1987_02
Patent number
US04640915

Reaction notes

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