Methyl iodide → Methyl 6-fluoropyridine-3-carboxylate

HRID 2173860Notes

Reaction equation

HRID 2173860 reaction equation
[C:1]([O-])([O-])=O.[K+].[K+].[F:7][C:8]1[CH:16]=[CH:15][C:11]([C:12]([OH:14])=[O:13])=[CH:10][N:9]=1.CI>CN(C)C=O>[CH3:1][O:13][C:12](=[O:14])[C:11]1[CH:15]=[CH:16][C:8]([F:7])=[N:9][CH:10]=1

Participants

5

Reactant 3

HCID 6328Methyl iodideHCID 11430Potassium CarbonateHCID 2428196-Fluoronicotinic Acid

Product 1

HCID 13758765Methyl 6-fluoropyridine-3-carboxylateYield 84%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

A round bottom flask was charged with K2CO3 (191 g, 1380 mmol), 6-fluoronicotinic acid (77.8 g, 551 mmol) and dimethylformamide (551 mL). Methyl iodide (51.5 mL, 827 mmol) was then added in one portion at room temperature and mixture stirred overnight at room temperature. The reaction mixture was partitioned between ethyl acetate and water. The organic layer was washed three times with water and once with brine, and then dried over Na2SO4. Purification by silica gel flash chromatography (ethyl acetate/dichloromethane) gave 6-fluoro-nicotinic acid methyl ester (71.8 g, 84%) as a white solid. 1H NMR (400 MHz, CDCl3, δ): 3.96 (s, 3H) 7.01 (dd, J=8.58, 2.93 Hz, 1H) 8.41 (ddd, J=8.49, 7.61, 2.44 Hz, 1H) 8.89 (d, J=2.34 Hz, 1H); MS (M+1): 156.1.

Workup

  1. customThe reaction mixture was partitioned between ethyl acetate and water
  2. washThe organic layer was washed three times with water
  3. dry with materialonce with brine, and then dried over Na2SO4
  4. customPurification by silica gel flash chromatography (ethyl acetate/dichloromethane)

Sources & evidence

ORD record
ord-85dd38302f634358adfc341114948e63
Source dataset
uspto-grants-2015_06
Patent number
US09056834B2

Reaction notes

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