Hydrochloric Acid → 5-Cyano-2-(difluoromethyl)nicotinic acid

HRID 59414Notes

Reaction equation

HRID 59414 reaction equation
[C:1]([C:3]1[CH:4]=[N:5][C:6]([CH:14]([F:16])[F:15])=[C:7]([CH:13]=1)[C:8]([O:10]CC)=[O:9])#[N:2].O.O[Li].O.Cl>C1COCC1>[C:1]([C:3]1[CH:4]=[N:5][C:6]([CH:14]([F:16])[F:15])=[C:7]([CH:13]=1)[C:8]([OH:10])=[O:9])#[N:2]

Participants

6

Reactant 4

HCID 313Hydrochloric AcidHCID 962WaterHCID 168937Lithium hydroxide, monohydrateHCID 71059720Ethyl 5-cyano-2-(difluoromethyl)nicotinate

Product 1

HCID 900191735-Cyano-2-(difluoromethyl)nicotinic acidYield 66.7%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

To a solution of ethyl 5-cyano-2-(difluoromethyl)nicotinate (1.2 g, 5.3 mmol) in THF:water (20 mL:5 mL) was added LiOH.H2O (0.267 g, 6.3 mmol) at 0° C. and the reaction mass was stirred for 40-60 minutes. The reaction mass was acidified with dil. HCl and extracted with ethyl acetate. The organic layer was separated, dried over anhydrous sodium sulphate and concentrated to afford 0.700 g of the desired product. 1H NMR (300 MHz, DMSO d6): δ 7.37-7.72 (t, J=53.7 Hz, 1H), 8.24 (s, 1H), 9.30 (s, 1H), 14.25 (br s, 1H); MS (m/z): 199.34 (M+H)+.

Workup

  1. extractionextracted with ethyl acetate
  2. customThe organic layer was separated
  3. dry with materialdried over anhydrous sodium sulphate
  4. concentrationconcentrated

Sources & evidence

ORD record
ord-c4931f022e3f440691f476ea4bc6d262
Source dataset
uspto-grants-2016_09
Patent number
US09439890B2

Reaction notes

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