Hydrochloric Acid → Methyl 5-bromo-6-(4-fluorophenyl)-2-isopropoxynicotinate

HRID 2272462Notes

Reaction equation

HRID 2272462 reaction equation
[OH-:1].[K+].[Br:3][C:4]1[C:5]([C:16]2[CH:21]=[CH:20][C:19]([F:22])=[CH:18][CH:17]=2)=[N:6][C:7]([O:12][CH:13]([CH3:15])[CH3:14])=[C:8]([CH:11]=1)[C:9]#N.Cl.[CH2:24]([OH:26])C>>[Br:3][C:4]1[C:5]([C:16]2[CH:21]=[CH:20][C:19]([F:22])=[CH:18][CH:17]=2)=[N:6][C:7]([O:12][CH:13]([CH3:15])[CH3:14])=[C:8]([CH:11]=1)[C:9]([O:26][CH3:24])=[O:1]

Participants

5

Reactant 4

HCID 313Hydrochloric AcidHCID 702EthanolHCID 14797Potassium HydroxideHCID 1179921785-Bromo-6-(4-fluorophenyl)-2-isopropoxynicotinonitrile

Product 1

HCID 117992295Methyl 5-bromo-6-(4-fluorophenyl)-2-isopropoxynicotinate

Procedure

An 8 M aqueous potassium hydroxide solution (22.1 mL) was added to a mixture of 5-bromo-6-(4-fluorophenyl)-2-isopropoxynicotinonitrile (5.92 g) and ethanol (50 mL), and the resultant mixture was stirred overnight at 100 C. The reaction mixture was neutralized with 6 M hydrochloric acid at 0 C, followed by extraction with ethyl acetate. The organic layer was dried over anhydrous magnesium sulfate, and then, the solvent was distilled off under reduced pressure. Potassium carbonate (4.88 g) and iodomethane (1.66 mL) were added to a mixture of the obtained residue and DMF (30 mL), and the mixture was stirred at 60 C for 30 minutes. Water was added to the reaction mixture, followed by extraction with ethyl acetate. The organic layer was washed with saturated saline and dried over anhydrous magnesium sulfate, and then, the solvent was distilled off under reduced pressure. The obtained residue was purified by silica gel column chromatography (hexane/ethyl acetate) to obtain the title compound (3.65 g).

Workup

  1. extractionfollowed by extraction with ethyl acetate
  2. dry with materialThe organic layer was dried over anhydrous magnesium sulfate
  3. distillationthe solvent was distilled off under reduced pressure
  4. additionPotassium carbonate (4.88 g) and iodomethane (1.66 mL) were added to a mixture of the obtained residue and DMF (30 mL)
  5. additionWater was added to the reaction mixture
  6. extractionfollowed by extraction with ethyl acetate
  7. washThe organic layer was washed with saturated saline
  8. dry with materialdried over anhydrous magnesium sulfate
  9. distillationthe solvent was distilled off under reduced pressure
  10. customThe obtained residue was purified by silica gel column chromatography (hexane/ethyl acetate)

Sources & evidence

ORD record
ord-043e35cbbed84ccabeda16b762e9d2c5
Source dataset
uspto-grants-2015_09
Patent number
US09120777B2

Reaction notes

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