Carbon Dioxide → 4-Chloro-1H-indole-7-carboxylic acid

HRID 855230ノート

反応式

HRID 855230 の反応式
Br[C:2]1[CH:3]=[CH:4][C:5]([Cl:11])=[C:6]2[C:10]=1[NH:9][CH:8]=[CH:7]2.C([Li])CCC.[C:17](=[O:19])=[O:18].O>C1COCC1.CCCCCC>[Cl:11][C:5]1[CH:4]=[CH:3][C:2]([C:17]([OH:19])=[O:18])=[C:10]2[C:6]=1[CH:7]=[CH:8][NH:9]2

参加物

7

反応物 4

HCID 280Carbon DioxideHCID 962WaterHCID 187528737-bromo-4-chloro-1H-indoleHCID 178418339Butyllithium

生成物 1

HCID 693468504-Chloro-1H-indole-7-carboxylic acid収率 67%

試薬・触媒・溶媒 2

HCID 8028Tetrahydrofuran溶媒HCID 8058Hexane溶媒

反応条件

温度
-78 °C

実験手順

560 mg (2.43 mmol) of 7-bromo-4-chloro-1H-indole were dissolved in 15 ml THF. The reaction mixture was cooled to −78° C. and 4.55 ml of a 1.6 M butyl lithium solution in hexane were added under nitrogen in such a way, that the temperature did not exceed a maximum of −70° C. The yellow solution was stirred at 0 to 5° C. after complete addition for 30 min. The reaction mixture was cooled to −78° C. and dry ice was added. The reaction mixture was warmed to rt, stirred for 15 min and poured onto 100 ml water. The aqueous layer was washed twice with diethyl ether, acidified with 1N aqueous HCl solution and extracted twice with diethyl ether. The combined organic layers were washed with saturated aqueous sodium chloride solution, dried over sodium sulfate, filtered and the solvent was evaporated. The crude residue was stirred with hexane for 15 min, filtered and dried to yield 319 mg (67%) of 4-chloro-1H-indole-7-carboxylic acid as an off-white solid. MS (ISP) 194.1 (M−H)−.

後処理

  1. customa maximum of −70° C
  2. additionafter complete addition for 30 min
  3. temperatureThe reaction mixture was cooled to −78° C.
  4. temperatureThe reaction mixture was warmed to rt
  5. stirringstirred for 15 min
  6. washThe aqueous layer was washed twice with diethyl ether
  7. extractionextracted twice with diethyl ether
  8. washThe combined organic layers were washed with saturated aqueous sodium chloride solution
  9. dry with materialdried over sodium sulfate
  10. filtrationfiltered
  11. customthe solvent was evaporated
  12. stirringThe crude residue was stirred with hexane for 15 min
  13. filtrationfiltered
  14. customdried

出典と根拠

ORDレコード
ord-1964761b3f1e4773a96114da799c9e90
出典データセット
uspto-grants-2007_08
特許番号
US07259183B2

反応ノート

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