Carbon Dioxide → 5-(trifluoromethyl)-1H-indole-7-carboxylic acid

HRID 855283ノート

反応式

HRID 855283 の反応式
Br[C:2]1[CH:3]=[C:4]([C:11]([F:14])([F:13])[F:12])[CH:5]=[C:6]2[C:10]=1[NH:9][CH:8]=[CH:7]2.[Li]CCCC.[C:20](=[O:22])=[O:21].O>C1COCC1.CCCCCC>[F:12][C:11]([F:14])([F:13])[C:4]1[CH:5]=[C:6]2[C:10](=[C:2]([C:20]([OH:22])=[O:21])[CH:3]=1)[NH:9][CH:8]=[CH:7]2

参加物

7

反応物 4

HCID 280Carbon DioxideHCID 962WaterHCID 575461357-Bromo-5-(trifluoromethyl)-1H-indoleHCID 178418339Butyllithium

生成物 1

HCID 693474115-(trifluoromethyl)-1H-indole-7-carboxylic acid収率 31%

試薬・触媒・溶媒 2

HCID 8028Tetrahydrofuran溶媒HCID 8058Hexane溶媒

反応条件

温度
2.5 °C

実験手順

584 mg of 7-bromo-5-trifluoromethyl-indole (2.2 mmol) were dissolved in 15 ml THF and 4.1 ml of a 1.6 molar solution of n-BuLi in hexane were added at −78° C. The reaction mixture was then allowed to warm to 0-5° C. and was stirred at this temperature for 30 min. Then it was cooled again to −78° C., dry ice was added and the mixture was allowed to warm to rt. After 15 min at rt it was poured into water and extracted twice with ether. The aqueous phase was then acidified with 1 N HCl solution and extracted several times with DCM. The combined DCM extracts were then washed with brine, dried with magnesium sulfate, filtered and the solvent was evaporated. The remaining residue was triturated with n-hexane. Final filtration yielded 157 mg (31%) of 5-trifluoromethyl-1H-indole-7-carboxylic acid as an off-white solid. 1H NMR (DMSO-d6, 300 MHz): δ 6.66 (m, 1H), 7.48 (m, 1H), 7.89 (s, 1H), 8.18 (s, 1H), 11.46 (br s, 1H), 13.48 (br s, 1H).

後処理

  1. temperatureThen it was cooled again to −78° C.
  2. temperatureto warm to rt
  3. extractionextracted twice with ether
  4. extractionextracted several times with DCM
  5. washThe combined DCM extracts were then washed with brine
  6. dry with materialdried with magnesium sulfate
  7. filtrationfiltered
  8. customthe solvent was evaporated
  9. customThe remaining residue was triturated with n-hexane
  10. filtrationFinal filtration

出典と根拠

ORDレコード
ord-b71269be1a87467c89d86be9847a4ac9
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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