Hydrochloric Acid → 5-Bromo-6-(2,2,2-trifluoroethoxy)-2-(trifluoromethyl)nicotinic acid

HRID 598244Notes

Reaction equation

HRID 598244 reaction equation
C([O:3][C:4](=[O:22])[C:5]1[CH:10]=[C:9]([Br:11])[C:8]([O:12][CH2:13][C:14]([F:17])([F:16])[F:15])=[N:7][C:6]=1[C:18]([F:21])([F:20])[F:19])C.O.[OH-].[Li+].Cl>O1CCCC1.O>[Br:11][C:9]1[C:8]([O:12][CH2:13][C:14]([F:15])([F:16])[F:17])=[N:7][C:6]([C:18]([F:21])([F:19])[F:20])=[C:5]([CH:10]=1)[C:4]([OH:22])=[O:3]

Participants

6

Reactant 3

HCID 313Hydrochloric AcidHCID 168937Lithium hydroxide, monohydrateHCID 866347975-Bromo-6-(2,2,2-trifluoro-ethoxy)-2-trifluoromethyl-nicotinic acid ethyl ester

Product 1

HCID 863463205-Bromo-6-(2,2,2-trifluoroethoxy)-2-(trifluoromethyl)nicotinic acidYield 99.8%

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 8028TetrahydrofuranSolvent

Procedure

5-Bromo-6-(2,2,2-trifluoro-ethoxy)-2-trifluoromethyl-nicotinic acid ethyl ester (244 g, 0.61 mol) was dissolved in a mixture of tetrahydrofuran (2100 mL) and water (700 mL). Lithiumhydroxid monohydrate (77 g, 1.85 mol) was added and the mixture was stirred and heated at reflux-temperature for 1.5 h. After cooling to room temperature the mixture was acidified with hydrochloric acid (2N, 750 mL). The mixture was extracted with diethylether (1×1500 mL, 1×1000 mL), and the organic phases were washed with brine (1000 mL). The organic phases were combined, dried with MgSO4 and the solvent was evaporated to give the title compound (224 g) as off-white solid; MS (ISP) 365.9, 367.9 (M−H).

Workup

  1. temperatureheated
  2. temperatureat reflux-temperature for 1.5 h
  3. extractionThe mixture was extracted with diethylether (1×1500 mL, 1×1000 mL)
  4. washthe organic phases were washed with brine (1000 mL)
  5. dry with materialdried with MgSO4
  6. customthe solvent was evaporated

Sources & evidence

ORD record
ord-2aff941e77774e48b22304a5381c4e01
Source dataset
uspto-grants-2011_03
Patent number
US07897621B2

Reaction notes

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