Methanol → Methyl 5-fluoropyridine-2-carboxylate

HRID 269727Notes

Reaction equation

HRID 269727 reaction equation
Br[C:2]1[CH:7]=[CH:6][C:5]([F:8])=[CH:4][N:3]=1.C(N(CC)CC)C.C[OH:17].[C]=O.C[CH2:21][O:22][CH2:23]C>C([O-])(=O)C.[Pd+2].C([O-])(=O)C.C1(P(C2C=CC=CC=2)[C-]2C=CC=C2)C=CC=CC=1.[C-]1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=C1.[Fe+2].CN(C=O)C>[F:8][C:5]1[CH:6]=[CH:7][C:2]([C:21]([O:22][CH3:23])=[O:17])=[N:3][CH:4]=1

Participants

9

Reactant 5

HCID 887MethanolHCID 3283Diethyl EtherHCID 8471TriethylamineHCID 27831712-Bromo-5-fluoropyridineHCID 178418416HCID 178418416, compound

Product 1

HCID 23053520Methyl 5-fluoropyridine-2-carboxylateYield 41%

Reagents, catalysts & solvents 3

HCID 167845palladium(II) acetateCatalystHCID 635956Ferrocene-1,1'-bis-(diphenylphosphine)CatalystHCID 6228DimethylformamideSolvent

Procedure

A mixture of 2-bromo-5-fluoropyridine (72.5 g, 412 mmol), palladium(II) acetate (2.5 g, 11.2 mmol), 1,1′-bis(diphenylphosphino)ferrocene (11.9 g, 21.5 mmol), triethylamine (100 mL), CH3OH (350 mL), and DMF (350 mL) were shaken in a pressure apparatus at 80° C. under 4.1 bar (60 psig) carbon monoxide overnight. The crude mixture was diluted with ether (3 L) and filtered through diatomaceous earth. The filtrate was washed with brine (3×500 mL), dried (Na2SO4), filtered and the solvent removed. Flash chromatography, using 10-25% ethyl acetate in hexanes, afforded 26.2 g (169 mmol, 41% yield) of methyl 5-fluoropyridine-2-carboxylate.

Workup

  1. filtrationfiltered through diatomaceous earth
  2. washThe filtrate was washed with brine (3×500 mL)
  3. dry with materialdried (Na2SO4)
  4. filtrationfiltered
  5. customthe solvent removed

Sources & evidence

ORD record
ord-5fecadca5c584c9c832fca26cf02c0bf
Source dataset
uspto-grants-2008_11
Patent number
US07449457B2

Reaction notes

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