Hydrochloric Acid → Methyl 6-(2-fluoro-5-methoxyphenyl)-5-isobutoxy-2-methoxynicotinate

HRID 709770Notes

Reaction equation

HRID 709770 reaction equation
Cl[C:2]1[N:11]=[C:10]([C:12]2[CH:17]=[C:16]([O:18][CH3:19])[CH:15]=[CH:14][C:13]=2[F:20])[C:9]([O:21][CH2:22][CH:23]([CH3:25])[CH3:24])=[CH:8][C:3]=1[C:4]([O:6][CH3:7])=[O:5].[CH3:26][O-:27].[Na+].Cl>C1COCC1.CO>[F:20][C:13]1[CH:14]=[CH:15][C:16]([O:18][CH3:19])=[CH:17][C:12]=1[C:10]1[C:9]([O:21][CH2:22][CH:23]([CH3:25])[CH3:24])=[CH:8][C:3]([C:4]([O:6][CH3:7])=[O:5])=[C:2]([O:27][CH3:26])[N:11]=1

Participants

6

Reactant 3

HCID 313Hydrochloric AcidHCID 10942334Sodium MethoxideHCID 117760273Methyl 2-chloro-6-(2-fluoro-5-methoxyphenyl)-5-isobutoxynicotinate

Product 1

HCID 117760172Methyl 6-(2-fluoro-5-methoxyphenyl)-5-isobutoxy-2-methoxynicotinate

Reagents, catalysts & solvents 2

HCID 887MethanolSolventHCID 8028TetrahydrofuranSolvent

Conditions

Temperature
60 °C

Procedure

Under a nitrogen atmosphere, to a solution of methyl 2-chloro-6-(2-fluoro-5-methoxyphenyl)-5-isobutoxynicotinate (248 mg) in THF (5.0 mL) was added a 28% solution of sodium methoxide in methanol (3.42 mL). The reaction mixture was stirred at room temperature for 1 hr and further at 60° C. for 48 hr. 6N Hydrochloric acid (0.44 mL) was added to the reaction mixture, and the resulting sodium chloride was filtered off. The solvent in the filtrate was evaporated under reduced pressure, and the residue was heated with conc. sulfuric acid (108 μL) and methanol (10 mL) under reflux for 3 hr. The reaction mixture was neutralized with sodium hydrogen carbonate, and the solvent in the reaction mixture was evaporated under reduced pressure and the residue was filtered. The solvent in the filtrate was evaporated under reduced pressure to give a crude product of the title compound (213 mg) as a yellow oil. This compound was used for the next step without further purification.

Workup

  1. filtrationthe resulting sodium chloride was filtered off
  2. customThe solvent in the filtrate was evaporated under reduced pressure
  3. temperaturethe residue was heated with conc. sulfuric acid (108 μL) and methanol (10 mL)
  4. temperatureunder reflux for 3 hr
  5. customthe solvent in the reaction mixture was evaporated under reduced pressure
  6. filtrationthe residue was filtered
  7. customThe solvent in the filtrate was evaporated under reduced pressure

Sources & evidence

ORD record
ord-92c13da0f3004e1bba048dd975fa8e4c
Source dataset
uspto-grants-2015_11
Patent number
US09181186B2

Reaction notes

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