Methyl iodide → Methyl 6-fluoropyridine-3-carboxylate

HRID 1427503Notes

Reaction equation

HRID 1427503 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-282e0e23f4df4411929bfe463caf1bfa
Source dataset
uspto-grants-2015_01
Patent number
US08933104B2

Reaction notes

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