Hydrochloric Acid → Ethyl 5-bromo-2-ethoxy-6-(4-fluorophenyl)nicotinate

HRID 531033Notes

Reaction equation

HRID 531033 reaction equation
[OH-:1].[K+].[Br:3][C:4]1[C:5]([C:15]2[CH:20]=[CH:19][C:18]([F:21])=[CH:17][CH:16]=2)=[N:6][C:7]([O:12][CH2:13][CH3:14])=[C:8]([CH:11]=1)[C:9]#N.C1C[O:25][CH2:24][CH2:23]1.Cl>C(O)C>[Br:3][C:4]1[C:5]([C:15]2[CH:20]=[CH:19][C:18]([F:21])=[CH:17][CH:16]=2)=[N:6][C:7]([O:12][CH2:13][CH3:14])=[C:8]([CH:11]=1)[C:9]([O:25][CH2:24][CH3:23])=[O:1]

Participants

6

Reactant 4

HCID 313Hydrochloric AcidHCID 8028TetrahydrofuranHCID 14797Potassium HydroxideHCID 1179921125-Bromo-2-ethoxy-6-(4-fluorophenyl)nicotinonitrile

Product 1

HCID 90424072Ethyl 5-bromo-2-ethoxy-6-(4-fluorophenyl)nicotinate

Reagents, catalysts & solvents 1

HCID 702EthanolSolvent

Conditions

Temperature
60 °C

Procedure

An 8 M aqueous potassium hydroxide solution (14.6 mL) was added to a mixture of 5-bromo-2-ethoxy-6-(4-fluorophenyl)nicotinonitrile (3.75 g), THF (10 mL), and ethanol (10 mL), and the resultant mixture was stirred overnight at 100° C. The reaction mixture was neutralized with 6 M hydrochloric acid, 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 (3.23 g) and iodoethane (1.40 mL) were added to a mixture of the obtained residue and DMF (10 mL), and the resultant 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 (2.40 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 (3.23 g) and iodoethane (1.40 mL) were added to a mixture of the obtained residue and DMF (10 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-5c20242c8fc94c4285971dbb8d63b014
Source dataset
uspto-grants-2016_05
Patent number
US09353108B2

Reaction notes

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