Hydrochloric Acid → 2-Chloro-5-fluoronicotinic acid

HRID 1827951Notes

Reaction equation

HRID 1827951 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-fluoronicotinate2×

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) (prepared according to the method of J. Med. Chem., 1993, 36(18), 2676–88, page 2684, column 2, 3rd example, ethyl-2-chloro-5-fluoropyridine-3-carboxylate) 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 pH 1 by addition of 6M hydrochloric acid and then extracted with dichloromethane (×3). 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 (×3)
  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-1ad098d124b74fea8b48b2c67f97a478
Source dataset
uspto-grants-2006_06
Patent number
US07056934B2

Reaction notes

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