Sulfolane → Methyl 6-bromo-1-(sec-butyl)-3-methyl-1H-indole-4-carboxylate

HRID 516767노트

반응식

HRID 516767 반응식
[Br:1][C:2]1[CH:3]=[C:4]([C:17]([O:19][CH3:20])=[O:18])[C:5]2[C:6]([CH:15]=O)=[CH:7][N:8]([CH:11]([CH2:13][CH3:14])[CH3:12])[C:9]=2[CH:10]=1.O.C1(C)C=CC(S(O)(=O)=O)=CC=1.S1(CCCC1)(=O)=O.C([BH3-])#N.[Na+]>CN(C=O)C.O>[Br:1][C:2]1[CH:3]=[C:4]([C:17]([O:19][CH3:20])=[O:18])[C:5]2[C:6]([CH3:15])=[CH:7][N:8]([CH:11]([CH2:13][CH3:14])[CH3:12])[C:9]=2[CH:10]=1

참가 물질

7

반응물 4

HCID 31347SulfolaneHCID 521998p-Toluenesulfonic acid monohydrateHCID 5003444Sodium cyanoborohydrideHCID 78358290Methyl 6-bromo-1-(sec-butyl)-3-formyl-1H-indole-4-carboxylate

생성물 1

HCID 67465536Methyl 6-bromo-1-(sec-butyl)-3-methyl-1H-indole-4-carboxylate수율 54.6%

시약·촉매·용매 2

HCID 962Water용매HCID 6228Dimethylformamide용매

반응 조건

온도
100 °C

실험 절차

To a stirred solution of methyl 6-bromo-1-sec-butyl-3-formyl-1H-indole-4-carboxylate (15 g, 44.6 mmol) in DMF (115 mL) was added p-toluenesulfonic acid mono hydrate (1.1 g, 5.8 mmol), p-toluenesulfonyl hydrazide (10.8 g, 58 mmol) followed by sulfolane (115 mL) at RT and the reaction mixture was stirred at 100° C. for 1 h. The reaction mixture was cooled to room temperature, treated with sodium cyanoborohydride (11.9 g, 178.5 mmol) portion wise over a period of 5 min and stirred at 100° C. for 2 h. The reaction mixture was cooled to room temperature and stirred at the same temperature for 16 h. The reaction mixture was diluted with water and extracted with 30% EtOAc: Pet ether. The organic layer was washed with cold water (100 mL), brine (100 mL) and dried over anhydrous Na2SO4 and concentrated under reduced pressure to afford crude, which was purified by column chromatography over silica gel (100-200 mesh) using 5% EtOAc: Pet ether as eluent to afford title compound methyl 6-bromo-1-sec-butyl-3-methyl-1H-indole-4-carboxylate (7.88 g, 54.6%) as pale yellow gum. 1H NMR (CDCl3, 400 MHz): δ 0.804-0.841 (t, J=7.4 Hz, 3H), 1.454-1.470 (d, J=6.4 Hz, 3H), 1.865-1.884 (m, 2H), 2.363 (s, 3H), 3.950 (s, 3H), 4.265-4.316 (m, 1H), 7.038 (s, 1H), 7.609 (d, J=1.2 Hz, 1H), 7.671 (d, J=2 Hz, 1H). MS (ES+): 324.19 [M+H] ion present.

후처리

  1. temperatureThe reaction mixture was cooled to room temperature
  2. stirringstirred at 100° C. for 2 h
  3. temperatureThe reaction mixture was cooled to room temperature
  4. stirringstirred at the same temperature for 16 h
  5. extractionextracted with 30% EtOAc
  6. washThe organic layer was washed with cold water (100 mL), brine (100 mL)
  7. dry with materialdried over anhydrous Na2SO4
  8. concentrationconcentrated under reduced pressure
  9. customto afford crude, which
  10. customwas purified by column chromatography over silica gel (100-200 mesh)

출처 및 근거

ORD 기록
ord-61e06ac675c647d2ab268f2fd01255fe
출처 데이터셋
uspto-grants-2015_08
특허 번호
US09114141B2

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