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

HRID 855283노트

반응식

HRID 855283 반응식
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

참가 물질

7

반응물 4

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

생성물 1

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

시약·촉매·용매 2

HCID 8028Tetrahydrofuran용매HCID 8058Hexane용매

반응 조건

온도
2.5 °C

실험 절차

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).

후처리

  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

출처 및 근거

ORD 기록
ord-b71269be1a87467c89d86be9847a4ac9
출처 데이터셋
uspto-grants-2007_08
특허 번호
US07259183B2

반응 노트

불러오는 중…