Acetic Acid → HCID 67464903, compound

HRID 2202778Notes

Reaction equation

HRID 2202778 reaction equation
C([Li])CCC.Br[C:7]1[C:12]([F:13])=[CH:11][CH:10]=[CH:9][N:8]=1.[C:14]([O:18][C:19]([N:21]1[CH:26]2[CH2:27][CH2:28][CH:22]1[CH2:23][C:24](=[O:29])[CH2:25]2)=[O:20])([CH3:17])([CH3:16])[CH3:15].C(O)(=O)C>C(OCC)C>[C:14]([O:18][C:19]([N:21]1[CH:26]2[CH2:27][CH2:28][CH:22]1[CH2:23][C:24]([C:7]1[C:12]([F:13])=[CH:11][CH:10]=[CH:9][N:8]=1)([OH:29])[CH2:25]2)=[O:20])([CH3:17])([CH3:15])[CH3:16]

Participants

6

Reactant 4

HCID 176Acetic AcidHCID 27628032-Bromo-3-fluoropyridineHCID 2794767tert-Butyl 3-oxo-8-azabicyclo(3.2.1)octane-8-carboxylateHCID 178418339Butyllithium

Product 1

HCID 67464903HCID 67464903, compoundYield 34.2%

Reagents, catalysts & solvents 1

HCID 3283Diethyl EtherSolvent2×

Procedure

n-Butyl lithium (2.5M, 1 mL, 2.5 mmol) was added dropwise to a solution of 2-bromo-3-fluoro-pyridine (0.4 g, 2.27 mmol) in diethyl ether (8 mL), under nitrogen at −78° C. and stirred for 1 hour. 3-Oxo-8-aza-bicyclo[3.2.1]octane-8-carboxylic acid tert-butyl ester (0.51 g, 2.27 mmol) in diethyl ether (5 mL) was added dropwise at −78° C. and the reaction mixture stirred for 0.5 hours before warming to room temperature. The reaction mixture was poured onto ice, acidified with acetic acid and extracted into ethyl acetate. The remaining aqueous solution was basified with 1 M sodium hydroxide, extracted with DCM and the combined organics were dried over magnesium sulphate, filtered and the solvent removed by evaporation under vacuum. Methanol (10 mL) and sodium borohydride (0.14 g) were added to the residues and stirred for 2 hours to reduce any unreacted ketone. The solvent was removed by evaporation under vacuum, DCM added to the residues and the organics washed with water and brine, dried over magnesium sulphate, filtered and the solvent removed by evaporation under vacuum. The residue was purified by flash chromatography on silica eluting with 5-10% ethyl acetate/cyclohexane. The fractions containing the desired product were concentrated under vacuum to give the title compound (0.25 g). LCMS m/z 323 [M+H]+. R.T.=4.67 min (Analytical Method 3).

Workup

  1. stirringthe reaction mixture stirred for 0.5 hours
  2. additionThe reaction mixture was poured onto ice
  3. extractionextracted into ethyl acetate
  4. extractionextracted with DCM
  5. dry with materialthe combined organics were dried over magnesium sulphate
  6. filtrationfiltered
  7. customthe solvent removed by evaporation under vacuum
  8. additionMethanol (10 mL) and sodium borohydride (0.14 g) were added to the residues
  9. stirringstirred for 2 hours
  10. customThe solvent was removed by evaporation under vacuum, DCM
  11. additionadded to the residues
  12. washthe organics washed with water and brine
  13. dry with materialdried over magnesium sulphate
  14. filtrationfiltered
  15. customthe solvent removed by evaporation under vacuum
  16. customThe residue was purified by flash chromatography on silica eluting with 5-10% ethyl acetate/cyclohexane
  17. additionThe fractions containing the desired product
  18. concentrationwere concentrated under vacuum

Sources & evidence

ORD record
ord-f941bad4168d46aa9fa9408afab20fcf
Source dataset
uspto-grants-2016_06
Patent number
US09365564B2

Reaction notes

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