Methanol → 4-(4-Bromo-2-fluorophenylamino)-5-fluoro-6-methoxy-nicotinic acid methyl ester

HRID 2111070Notes

Reaction equation

HRID 2111070 reaction equation
[CH3:1][O-:2].[Na+].[CH3:4][O:5][C:6](=[O:24])[C:7]1[C:12]([NH:13][C:14]2[CH:19]=[CH:18][C:17]([Br:20])=[CH:16][C:15]=2[F:21])=[C:11]([F:22])[C:10](Cl)=[N:9][CH:8]=1.CO>C1COCC1>[CH3:4][O:5][C:6](=[O:24])[C:7]1[C:12]([NH:13][C:14]2[CH:19]=[CH:18][C:17]([Br:20])=[CH:16][C:15]=2[F:21])=[C:11]([F:22])[C:10]([O:2][CH3:1])=[N:9][CH:8]=1

Participants

5

Reactant 3

HCID 887MethanolHCID 10942334Sodium MethoxideHCID 866015274-(4-Bromo-2-fluorophenylamino)-6-chloro-5-fluoro-nicotinic acid methyl ester

Product 1

HCID 666740814-(4-Bromo-2-fluorophenylamino)-5-fluoro-6-methoxy-nicotinic acid methyl ester

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

Sodium methoxide (2.20 g, 40.8 mmol) was slowly added to a stirred solution of 4-(4-bromo-2-fluorophenylamino)-6-chloro-5-fluoro-nicotinic acid methyl ester in 4:1 MeOH:THF (20 mL) at 0° C. The reaction mixture was warmed to room temperature, stirred for 17 hours and then warmed to 40° C. and stirred for 5 hours. After cooling to room temperature, the reaction mixture was quenched with water and extracted with ethyl acetate. The combined organic extracts were dried (MgSO4) and concentrated under reduced pressure. The desired product, contaminated with some starting material, was carried forward without purification.

Workup

  1. customat 0° C
  2. temperaturewarmed to 40° C.
  3. stirringstirred for 5 hours
  4. temperatureAfter cooling to room temperature
  5. customthe reaction mixture was quenched with water
  6. extractionextracted with ethyl acetate
  7. dry with materialThe combined organic extracts were dried (MgSO4)
  8. concentrationconcentrated under reduced pressure
  9. customwas carried forward without purification

Sources & evidence

ORD record
ord-bf6aa638608a48b2a3cd7fb6d5b24e59
Source dataset
uspto-grants-2009_04
Patent number
US07517994B2

Reaction notes

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