Dimethyl Sulfate → Benzyl 3-methoxy-1-azabicyclo[3.2.0]hept-2-en-7-one-2-carboxylate

HRID 620433Notes

Reaction equation

HRID 620433 reaction equation
[N:1]12[C:7](=[O:8])[CH2:6][CH:5]1[CH2:4][C:3](=[O:9])[CH:2]2[C:10]([O:12][CH2:13][C:14]1[CH:19]=[CH:18][CH:17]=[CH:16][CH:15]=1)=[O:11].S(OC)(O[CH3:24])(=O)=O.[H-].[Na+]>CN(C)P(N(C)C)(N(C)C)=O>[CH3:24][O:9][C:3]1[CH2:4][CH:5]2[N:1]([C:7](=[O:8])[CH2:6]2)[C:2]=1[C:10]([O:12][CH2:13][C:14]1[CH:19]=[CH:18][CH:17]=[CH:16][CH:15]=1)=[O:11]

Participants

5

Reactant 3

HCID 6497Dimethyl SulfateHCID 24758Sodium hydrideHCID 12804725Benzyl 3,7-dioxo-1-azabicyclo[3.2.0]heptane-2-carboxylate

Product 1

HCID 15136299Benzyl 3-methoxy-1-azabicyclo[3.2.0]hept-2-en-7-one-2-carboxylateYield 20.5%

Reagents, catalysts & solvents 1

HCID 12679HexamethylphosphoramideSolvent

Procedure

A solution of benzyl 1-azabicyclo[3.2.0]heptan-3,7-dione-2-carboxylate (25.9 mg, 0.1 mMol) in anhydrous hexamethylphosphoramide (1.0 ml) is cooled in an ice-bath and stirred under a nitrogen atmosphere. Dimethyl sulfate (11.4 μl, 0.12 mMol) and 57% sodium hydride in mineral oil (5.0 mg, 0.12 mMol) are added to the solution. The cooling bath is removed and the resulting mixture is stirred at room temperature for 60 minutes. The mixture is diluted with ethyl acetate (10 ml) and water (20 ml), shaken, and the layers separated. The organic layer is washed with water (3×5 ml) and brine, dried with magnesium sulfate, diluted with toluene (10 ml), and evaporated under vacuum to an oil. This material is chromatographed on a 0.25 mm×10×20 cm silica gel GF plate using 3:1 toluene-ethyl acetate as developing solvent. The major UV visible band at Rf 0.1 was removed and eluted with ethyl acetate to provide benzyl 3 -methoxy-1-azabicyclo[3.2.0]hept-2-en-7-one-2-carboxylate (5.6 mg) as a clear oil: IR (CH2Cl2) 1775 and 1700 cm-1 ; UV (EtOAc) 288 nm; NMR (CDCl3) δ 2.87 (dd, 1, J=2.8 and 16, H6β), 3.03 (m, 2, H4a and H4b), 3.50 (dd, 1, J=5.5 and 16, H6α), 3.80 (m, 1, H5), 3.92 (s, 3, CH3), 5.28 (s, 2, CH2 φ), and 7.40 (m, 5, C6H5); mass spectrum m/e 273 (M+) and 231 (M+-42).

Workup

  1. customThe cooling bath is removed
  2. stirringthe resulting mixture is stirred at room temperature for 60 minutes
  3. additionThe mixture is diluted with ethyl acetate (10 ml) and water (20 ml)
  4. stirringshaken
  5. customthe layers separated
  6. washThe organic layer is washed with water (3×5 ml) and brine
  7. dry with materialdried with magnesium sulfate
  8. additiondiluted with toluene (10 ml)
  9. customevaporated under vacuum to an oil
  10. customThis material is chromatographed on a 0.25 mm×10×20 cm silica gel GF plate
  11. customThe major UV visible band at Rf 0.1 was removed
  12. washeluted with ethyl acetate

Sources & evidence

ORD record
ord-3ba636c86c744c3db0cdf0553a9d1bcf
Source dataset
uspto-grants-1989_04
Patent number
US04820817

Reaction notes

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