Hydrochloric Acid → 2-Chloro-5-fluoronicotinic acid

HRID 724255Notes

Reaction equation

HRID 724255 reaction equation
C([O:3][C:4](=[O:13])[C:5]1[CH:10]=[C:9]([F:11])[CH:8]=[N:7][C:6]=1[Cl:12])C.[OH-].[Li+].Cl>O1CCCC1>[Cl:12][C:6]1[N:7]=[CH:8][C:9]([F:11])=[CH:10][C:5]=1[C:4]([OH:13])=[O:3]

Participants

5

Reactant 3

HCID 313Hydrochloric AcidHCID 3939Lithium HydroxideHCID 11390082Ethyl 2-chloro-5-fluoronicotinate

Product 1

HCID 114352432-Chloro-5-fluoronicotinic acid

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

Ethyl-2-chloro-5-fluoro-nicotinoate (50.4 g, 0.247 mol) (J. Med. Chem., 1993, 36(18), 2676–88) was dissolved in tetrahydrofuran (350 mL) and a 2M aqueous solution of lithium hydroxide (247 mL, 0.495 mol) added. The reaction mixture was stirred at room temperature for 3 days. The pH of the solution was reduced to pH1 by addition of 6M hydrochloric acid and then extracted with dichloromethane (x3). The combined extracts were dried over magnesium sulphate and the solvent concentrated in vacuo to give a solid which was triturated with diethyl ether and then dried to give the title compound as a white solid, 40.56 g.

Workup

  1. extractionextracted with dichloromethane (x3)
  2. dry with materialThe combined extracts were dried over magnesium sulphate
  3. concentrationthe solvent concentrated in vacuo
  4. customto give a solid which
  5. customwas triturated with diethyl ether
  6. customdried

Sources & evidence

ORD record
ord-9f96d56e5cb9485e84db85d9d24dec78
Source dataset
uspto-grants-2006_11
Patent number
US07141586B2

Reaction notes

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