Hydrochloric Acid → Methyl 2-fluoro-6-methoxynicotinate

HRID 1721571Notes

Reaction equation

HRID 1721571 reaction equation
[F:1][C:2]1[C:7]([C:8]([O:10][CH3:11])=[O:9])=[CH:6][CH:5]=[C:4](F)[N:3]=1.[CH3:13][O-:14].[Na+].Cl>O1CCCC1.CO>[F:1][C:2]1[C:7]([C:8]([O:10][CH3:11])=[O:9])=[CH:6][CH:5]=[C:4]([O:14][CH3:13])[N:3]=1

Participants

6

Reactant 3

HCID 313Hydrochloric AcidHCID 108449402,6-Difluoro-nicotinic acid methyl esterHCID 10942334Sodium Methoxide

Product 1

HCID 10821376Methyl 2-fluoro-6-methoxynicotinate

Reagents, catalysts & solvents 2

HCID 887MethanolSolventHCID 8028TetrahydrofuranSolvent

Procedure

To a stirred solution of 15.0 g (0.0867 mol) of the product from Example 12 in 240 mL dry tetrahydrofuran cooled to -78° was added dropwise 22.7 mL (0.0993 mol) of 25% sodium methoxide in methanol solution over 45 minutes. After warming to -20° the mixture was poured into ice water, acidified with 1 normal hydrochloric acid and extracted with ether. The combined organic layers were washed with brine, dried over magnesium sulfate, and evaporated to a semisolid which was purified by flash chromatography to afford 3.2 g (17%) light yellow solid: m.p. 81°-82°; NMR (CDCl3, 200 MHz) 3.9 (3H, s), 3.98 (3H, s), 6.67 (1H, d, J=9 Hz), 8.25 (1H, m); IR (nujol) 1715, 1615, 1290 cm-1.

Workup

  1. temperatureAfter warming to -20° the mixture
  2. extractionextracted with ether
  3. washThe combined organic layers were washed with brine
  4. dry with materialdried over magnesium sulfate
  5. customevaporated to a semisolid which
  6. customwas purified by flash chromatography
  7. customto afford 3.2 g (17%) light yellow solid

Sources & evidence

ORD record
ord-0ebc3b03f29742fb8757bc26c75a19c2
Source dataset
uspto-grants-1996_04
Patent number
US05512535

Reaction notes

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