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

HRID 235736Notes

Reaction equation

HRID 235736 reaction equation
[CH3:1][C:2]1([CH3:13])[O:9][CH2:8][CH2:7][C@H:6]2[N:3]1[C:4](=[O:12])[C@@H:5]2[N+:10]#[C-:11].C([Li])CCC.[CH3:19][C:20]([CH3:22])=[O:21].C(O)(=O)C>O1CCCC1.CCCCCC>[CH3:1][C:2]1([CH3:13])[O:9][CH2:8][CH2:7][C@H:6]2[N:3]1[C:4](=[O:12])[C@@:5]2([C:20]([OH:21])([CH3:22])[CH3:19])[N+:10]#[C-:11]

Participants

7

Reactant 4

HCID 176Acetic AcidHCID 180AcetoneHCID 54269083(6R,7R)-2,2-dimethyl-7-isocyano-1-aza-3-oxabicyclo[4.2.0]octan-8-oneHCID 178418339Butyllithium

Product 1

HCID 53810652(6R,7R)-2,2-dimethyl-7-(1-hydroxy-1-methylethyl)-7-isocyano-1-aza-3-oxabicyclo[4.2.0]octan-8-one

Reagents, catalysts & solvents 2

HCID 8028TetrahydrofuranSolvent2×HCID 8058HexaneSolvent

Conditions

Temperature
-70 °C

Procedure

To a solution of (6R,7R)-2,2-dimethyl-7-isocyano-1-aza-3-oxabicyclo[4.2.0]octan-8-one (500 mg) in tetrahydrofuran (15 ml) was added a solution of n-butyllithium in hexane (2.33 ml of 1.55M solution) at -70° C. and the mixture was stirred at -70° C. for 15 minutes. A solution of acetone (0.265 ml) in tetrahydrofuran (2.4 ml) was added to the reaction mixture at -70° C. and the mixture was stirred at -70° C. for 25 minutes. Acetic acid (0.477 ml) was added to the mixture at -70° C. After stirring at -70° C. for 20 minutes, the mixture was evaporated in vacuo. The residue was dissolved in ethyl acetate (80 ml) and the solution was washed with aqueous sodium bicarbonate. The aqueous layer was separated and extracted with ethyl acetate (20 ml). The combined organic layers were washed with brine, dried over magnesium sulfate, and evaporated in vacuo. The crystalline residue was washed with isopropyl ether and filtered to give (6R,7R)-2,2-dimethyl-7-(1-hydroxy-1-methylethyl)-7-isocyano-1-aza-3-oxabicyclo[4.2.0]octan-8-one (460 mg). The mother liquor was chromatographed on silica gel (5 g) eluting with a mixture of hexane and ethyl acetate (20:1-1:1) to give additional (6R,7R)-2,2-dimethyl-7-(1-hydroxy-1-methylethyl)-7-isocyano-1-aza-3-oxabicyclo[4.2.0]octan-8-one (65 mg) [(6R,7R)-isomer] and its (6R,7S)-isomer (103 mg).

Workup

  1. stirringthe mixture was stirred at -70° C. for 25 minutes
  2. stirringAfter stirring at -70° C. for 20 minutes
  3. customthe mixture was evaporated in vacuo
  4. dissolutionThe residue was dissolved in ethyl acetate (80 ml)
  5. washthe solution was washed with aqueous sodium bicarbonate
  6. customThe aqueous layer was separated
  7. extractionextracted with ethyl acetate (20 ml)
  8. washThe combined organic layers were washed with brine
  9. dry with materialdried over magnesium sulfate
  10. customevaporated in vacuo
  11. washThe crystalline residue was washed with isopropyl ether
  12. filtrationfiltered

Sources & evidence

ORD record
ord-8dda404d938f46d0a46c503073e605f5
Source dataset
uspto-grants-1987_02
Patent number
US04640915

Reaction notes

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