Methanol → Methyl 6-(cyclopropylmethoxy)-5-fluoronicotinate
Reaction equation
Br[C:2]1[CH:3]=[C:4]([F:13])[C:5]([O:8][CH2:9][CH:10]2[CH2:12][CH2:11]2)=[N:6][CH:7]=1.C(N(CC)CC)C.[CH3:21][OH:22].CN([CH:26]=[O:27])C>C1C=CC(P(C2C=CC=CC=2)[C-]2C=CC=C2)=CC=1.C1C=CC(P(C2C=CC=CC=2)[C-]2C=CC=C2)=CC=1.Cl[Pd]Cl.[Fe+2].ClCCl.O>[CH:10]1([CH2:9][O:8][C:5]2[C:4]([F:13])=[CH:3][C:2]([C:21]([O:27][CH3:26])=[O:22])=[CH:7][N:6]=2)[CH2:12][CH2:11]1Participants
7
Reactant 4
Product 1
Reagents, catalysts & solvents 2
Conditions
- Temperature
- 80 °C
Procedure
A mixture of 5-bromo-2-(cyclopropylmethoxy)-3-fluoropyridine (2.49 g), [1,1′-bis(diphenylphosphino)ferrocene]dichloropalladium(II) dichloromethane adduct (832 mg), triethylamine (2.82 mL), methanol (2 mL) and DMF (20 mL) was stirred overnight at 80° C. under a carbon monoxide atmosphere. To the reaction mixture was added water, and the mixture was extracted with ethyl acetate. The organic layer was washed with saturated brine, and dried over anhydrous magnesium sulfate, and the solvent was evaporated under reduced pressure. The residue was purified by silica gel column chromatography (hexane/ethyl acetate) to give the title compound (1.75 g).
Workup
- extractionthe mixture was extracted with ethyl acetate
- washThe organic layer was washed with saturated brine
- dry with materialdried over anhydrous magnesium sulfate
- customthe solvent was evaporated under reduced pressure
- customThe residue was purified by silica gel column chromatography (hexane/ethyl acetate)
Sources & evidence
- ORD record
- ord-42e0d4e0829042b6aa5359161b811fac
- Source dataset
- uspto-grants-2015_09
- Patent number
- US09133129B2
Reaction notes
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