Hydrochloric Acid → 2-Chloro-5-fluoronicotinic acid

HRID 1828837Notes

Reaction equation

HRID 1828837 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 acidYield 93.5%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

Ethyl-2-chloro-5-fluoro-nicotinoate (50.4 g, 0.247 mol) (see reference J. Med. Chem., 1993, 36(18), 2676–88) was dissolved in tetrahydrofuran (350 ml) and a 2 M 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 6 N hydrochloric acid and then extracted with dichloromethane (3 fold). The combined extracts were dried over anhydrous magnesium sulphate and the solvent removed in vacuo to give a solid which was triturated with diethyl ether and then dried in vacuo to give 2-chloro-5-fluoro nicotinic acid (40.56 g) as a white solid. 1H NMR (400 MHz, DMSO-d6): δ=8.20 (1H, s), 8.62 (1H, s) ppm. LRMS (electrospray): m/z [M+H]+ 174.

Workup

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

Sources & evidence

ORD record
ord-15f91d5bbffb4728a030bd3d3fec93a4
Source dataset
uspto-grants-2006_06
Patent number
US07060717B2

Reaction notes

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