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

HRID 1378293노트

반응식

HRID 1378293 반응식
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]

참가 물질

6

반응물 4

HCID 6228DimethylformamideHCID 24758Sodium hydrideHCID 4485645-[4-bromo-1-methyl-5-(trifluoromethyl)-1H-pyrazol-3-yl]-2-chloro-4-fluorobenzoic acidHCID 178418339Butyllithium2회

생성물 1

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

시약·촉매·용매 1

HCID 8028Tetrahydrofuran용매

반응 조건

온도
60 °C

실험 절차

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.

후처리

  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

출처 및 근거

ORD 기록
ord-8020391c55b4407eba524591426fc5c5
출처 데이터셋
uspto-grants-1997_09
특허 번호
US05668088

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