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

HRID 1488741ノート

反応式

HRID 1488741 の反応式
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]

参加物

6

反応物 4

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

生成物 1

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

試薬・触媒・溶媒 1

HCID 8028Tetrahydrofuran溶媒

反応条件

温度
60 °C

実験手順

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 400ml 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.

後処理

  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

出典と根拠

ORDレコード
ord-43ef898fd30e4061b8c05b2f988ef1df
出典データセット
uspto-grants-1997_10
特許番号
US05675017

反応ノート

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