2,2'-Bipyridine → 4-Bromo-1-cyclopropylpyridin-2(1H)-one

HRID 1191846Notes

Reaction equation

HRID 1191846 reaction equation
[Br:1][C:2]1[CH:7]=[CH:6][NH:5][C:4](=[O:8])[CH:3]=1.[CH:9]1(B(O)O)[CH2:11][CH2:10]1.N1C=CC=CC=1C1C=CC=CN=1.C([O-])([O-])=O.[Na+].[Na+].[NH4+].[Cl-]>CC([O-])=O.CC([O-])=O.[Cu+2].ClCCCl>[Br:1][C:2]1[CH:7]=[CH:6][N:5]([CH:9]2[CH2:11][CH2:10]2)[C:4](=[O:8])[CH:3]=1

Participants

8

Reactant 5

HCID 14742,2'-BipyridineHCID 10340Sodium Carbonate2×HCID 25517Ammonium ChlorideHCID 8171154-Bromo-2-hydroxypyridineHCID 2760897Cyclopropylboronic acid2×

Product 1

HCID 596356474-Bromo-1-cyclopropylpyridin-2(1H)-one

Reagents, catalysts & solvents 2

HCID 8895Cupric acetateCatalystHCID 111,2-DichloroethaneSolvent

Procedure

A flask charged with a stir bar, 4-bromo-1H-pyridin-2-one (1.80 g), cyclopropylboronic acid (2.00 g), Cu(OAc)2 (2.00 g), 2,2′-bipyridine (1.70 g), Na2CO3 (2.47 g), and 1,2-dichloroethane (75 mL) was heated to 70° C. and the mixture was stirred at this temperature in air overnight. Then, another portion of cyclopropylboronic acid (0.50 g) and Na2CO3 (0.55 g) were added and the mixture was further stirred at reflux temperature for another 4 h. After cooling to ambient temperature, aqueous NH4Cl solution was added and the resultant mixture was extracted with dichloromethane. The combined organic extracts were dried (MgSO4) and the solvent was evaporated. The residue was purified by chromatography on silica gel (cyclohexane/ethyl acetate 50:50->35:65) to afford the title compound as an oil that crystallized on standing. Yield: 0.82 g (37% of theory); Mass spectrum (ESI+): m/z=214/216 (Br) [M+H]+.

Workup

  1. additionA flask charged with a stir bar
  2. stirringthe mixture was further stirred
  3. temperatureat reflux temperature for another 4 h
  4. extractionthe resultant mixture was extracted with dichloromethane
  5. dry with materialThe combined organic extracts were dried (MgSO4)
  6. customthe solvent was evaporated
  7. customThe residue was purified by chromatography on silica gel (cyclohexane/ethyl acetate 50:50->35:65)

Sources & evidence

ORD record
ord-6ff25ae780ef447883d6cbc87d30b323
Source dataset
uspto-grants-2014_03
Patent number
US08680093B2

Reaction notes

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