Acetic Acid → HCID 67462773, compound

HRID 2202792Notes

Reaction equation

HRID 2202792 reaction equation
[O:1]1[CH:5]=[CH:4][N:3]=[CH:2]1.C([Li])CCC.[C:11]([O:15][C:16]([N:18]1[CH:23]2[CH2:24][CH2:25][CH:19]1[CH2:20][C:21](=[O:26])[CH2:22]2)=[O:17])([CH3:14])([CH3:13])[CH3:12].C(O)(=O)C>C1COCC1>[C:11]([O:15][C:16]([N:18]1[CH:23]2[CH2:24][CH2:25][CH:19]1[CH2:20][C:21]([OH:26])([C:2]1[O:1][CH:5]=[CH:4][N:3]=1)[CH2:22]2)=[O:17])([CH3:14])([CH3:12])[CH3:13]

Participants

6

Reactant 4

HCID 176Acetic AcidHCID 9255OxazoleHCID 2794767tert-Butyl 3-oxo-8-azabicyclo(3.2.1)octane-8-carboxylateHCID 178418339Butyllithium

Product 1

HCID 67462773HCID 67462773, compoundYield 34%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent2×

Procedure

Borane-THF complex (1M, 4.5 mL, 4.5 mmol) was added to a solution of oxazole (0.3 mL, 4.5 mmol) in THF (5 mL) and stirred for 1 hour under nitrogen before cooling to −78° C. n-Butyl lithium (2.5M, 1.8 mL, 4.5 mmol) was added and the reaction mixture stirred for a further 30 minutes. A solution of 3-oxo-8-aza-bicyclo[3.2.1]octane-8-carboxylic acid tert-butyl ester (0.675 g, 3.0 mmol) in THF (5 mL) was added and the reaction mixture stirred for 30 minutes. 10% acetic acid in IMS (10 mL) was added and the reaction mixture warmed to room temperature and then further to 40° C. for 30 minutes. The solvent was removed by evaporation under vacuum, water and ethyl acetate were added to the residues, the organics extracted, dried over magnesium sulphate, filtered and evaporated to dryness. The residue was purified by flash chromatography on silica eluting with 25-60% ethyl acetate/cyclohexane. The fractions containing the desired product were concentrated under vacuum to give the title compound (0.3 g) as a colourless oil. LCMS m/z 295.2 [M+H]+. R.T.=3.07 min (Analytical Method 3).

Workup

  1. additionwas added
  2. stirringthe reaction mixture stirred for a further 30 minutes
  3. stirringthe reaction mixture stirred for 30 minutes
  4. waitfurther to 40° C. for 30 minutes
  5. customThe solvent was removed by evaporation under vacuum, water and ethyl acetate
  6. additionwere added to the residues
  7. dry with materialthe organics extracted, dried over magnesium sulphate
  8. filtrationfiltered
  9. customevaporated to dryness
  10. customThe residue was purified by flash chromatography on silica eluting with 25-60% ethyl acetate/cyclohexane
  11. additionThe fractions containing the desired product
  12. concentrationwere concentrated under vacuum

Sources & evidence

ORD record
ord-f4e80fe756d142eca4b52dcc13b2237f
Source dataset
uspto-grants-2016_06
Patent number
US09365564B2

Reaction notes

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