Dimethylformamide → 2-chloro-4-fluoro-5-[4-formyl-1-methyl-5-(trifluoromethyl)-1H-pyrazol-3-yl]benzoic acid

HRID 1378293Notes

Reaction equation

HRID 1378293 reaction equation
Br[C:2]1[C:3]([C:12]2[C:13]([F:22])=[CH:14][C:15]([Cl:21])=[C:16]([CH:20]=2)[C:17]([OH:19])=[O:18])=[N:4][N:5]([CH3:11])[C:6]=1[C:7]([F:10])([F:9])[F:8].[H-].[Na+].C([Li])CCC.CN(C)[CH:32]=[O:33]>O1CCCC1>[Cl:21][C:15]1[CH:14]=[C:13]([F:22])[C:12]([C:3]2[C:2]([CH:32]=[O:33])=[C:6]([C:7]([F:10])([F:9])[F:8])[N:5]([CH3:11])[N:4]=2)=[CH:20][C:16]=1[C:17]([OH:19])=[O:18]

Participants

6

Reactant 4

HCID 6228DimethylformamideHCID 24758Sodium hydrideHCID 4485645-[4-bromo-1-methyl-5-(trifluoromethyl)-1H-pyrazol-3-yl]-2-chloro-4-fluorobenzoic acidHCID 178418339Butyllithium2×

Product 1

HCID 229064152-chloro-4-fluoro-5-[4-formyl-1-methyl-5-(trifluoromethyl)-1H-pyrazol-3-yl]benzoic acid

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Conditions

Temperature
60 °C

Procedure

To a mechanically stirred solution of 10 g of 5-[4-bromo-1-methyl-5-(trifluoromethyl)-1H-pyrazol-3-yl]-2-chloro-4-fluorobenzoic acid in 400 ml of anhydrous tetrahydrofuran under a nitrogen atmosphere was added 1.0 g of 95% sodium hydride. After the foaming subsided, the reaction was stirred and heated to 60° C. for one hour to ensure complete anion formation of the acid. The reaction was cooled to -110° C. with vigorous stirring and a 10.8 mL of 2.5M n-butyl lithium in hexanes was added maintaining the temperature below -100° C. As soon as the addition of n-butyl lithium was completed, 10 mL of dimethyl formamide was added and the solution was allowed to warm to -20° C. The reaction was then quenched with 3N HCl, and most of the volatiles were removed from the reaction mixture. The precipitate was filtered and recrystalized from carbon tetrachloride to give 3.0 g of 2-chloro-4-fluoro-5-[4-formyl-1-methyl-5-(trifluoromethyl)-1H-pyrazol-3-yl]benzoic acid: mp 163° C.; 1HNMR (CDCl3) ppm: 9.82 (s, 1H), 7.89 (d, 1H, J=7.6), 7.07 (d, 1H, J=9.2), 3.39 (s, 3H). 19FNMR (CDCl3) ppm: -57.78, -107.41.

Workup

  1. temperatureThe reaction was cooled to -110° C.
  2. stirringwith vigorous stirring
  3. temperaturemaintaining the temperature below -100° C
  4. temperatureto warm to -20° C
  5. customThe reaction was then quenched with 3N HCl
  6. custommost of the volatiles were removed from the reaction mixture
  7. filtrationThe precipitate was filtered
  8. customrecrystalized from carbon tetrachloride

Sources & evidence

ORD record
ord-8020391c55b4407eba524591426fc5c5
Source dataset
uspto-grants-1997_09
Patent number
US05668088

Reaction notes

Loading…