Sulfolane → methyl 6-bromo-1-isopropyl-3-methyl-1H-indole-4-carboxylate

HRID 42505노트

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HRID 42505 반응식
[Br:1][C:2]1[CH:3]=[C:4]([C:16]([O:18][CH3:19])=[O:17])[C:5]2[C:6]([CH:14]=O)=[CH:7][N:8]([CH:11]([CH3:13])[CH3:12])[C:9]=2[CH:10]=1.C1(C)C=CC(S(=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:16]([O:18][CH3:19])=[O:17])[C:5]2[C:6]([CH3:14])=[CH:7][N:8]([CH:11]([CH3:12])[CH3:13])[C:9]=2[CH:10]=1

참가 물질

7

반응물 4

HCID 31347SulfolaneHCID 5003444Sodium cyanoborohydrideHCID 86677357methyl 6-bromo-3-formyl-1-isopropyl-1H-indole-4-carboxylateHCID 178427284HCID 178427284, 화합물

생성물 1

HCID 67464634methyl 6-bromo-1-isopropyl-3-methyl-1H-indole-4-carboxylate수율 89.2%

시약·촉매·용매 2

HCID 962Water용매HCID 6228Dimethylformamide용매

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온도
100 °C

실험 절차

To a stirred solution of methyl 6-bromo-3-formyl-1-isopropyl-1H-indole-4-carboxylate (60 g, 185 mmol) in DMF (220 mL) was added p-toluenesulfonic acid mono hydride (4.57 g, 24 mmol), p-toluenesulfonyl hydrazide (44.8 g, 240 mmol) followed by sulfolane (220 mL). The mixture was stirred at 100° C. for 1 h. The contents were cooled to room temperature and then sodium cyanoborohydride (46.5 g, 740 mmol) was added portion wise over a period of 25 min. Then the mixture was stirred at 100° C. for 2 h. Then the reaction mixture was stirred for 16 h at room temperature. The reaction mixture was diluted with water and extracted with 20% EtOAc: Pet ether, finally organic layer was washed with cold water, brine solution dried over anhydrous Na2SO4 and concentrated. Crude compound was purified by column chromatography using silica gel (100-200 mesh) and 20% DCM: Pet ether as an eluent to afford desired product methyl 6-bromo-1-isopropyl-3-methyl-1H-indole-4-carboxylate (24 g, 89.2% purity), (16 g, and 62.2% purity). 1H NMR (CDCl3, 400 MHz) δ 1.486 (d, J=6.4 Hz, 6H), 2.361 (s, 3H), 3.947 (s, 3H), 4.535-4.602 (m, 1H), 7.080 (s, 1H), 7.619 (s, 1H), 7.684 (s, 1H). LCMS (ES+) m/z=310.07 (M+H)

후처리

  1. temperatureThe contents were cooled to room temperature
  2. stirringThen the mixture was stirred at 100° C. for 2 h
  3. stirringThen the reaction mixture was stirred for 16 h at room temperature
  4. extractionextracted with 20% EtOAc
  5. washPet ether, finally organic layer was washed with cold water, brine solution
  6. dry with materialdried over anhydrous Na2SO4
  7. concentrationconcentrated
  8. customCrude compound was purified by column chromatography

출처 및 근거

ORD 기록
ord-e9d49779bb894004b06fed95826ce42e
출처 데이터셋
uspto-grants-2013_09
특허 번호
US08536179B2

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