Methanesulfonic Acid → 5-((tert-Butyldimethylsilyl)oxy)-3-iodo-1-(tetrahydro-2H-pyran-2-yl)-1H-indazole

HRID 41513노트

반응식

HRID 41513 반응식
[Si:1]([O:8][C:9]1[CH:10]=[C:11]2[C:15](=[CH:16][CH:17]=1)[NH:14][N:13]=[C:12]2[I:18])([C:4]([CH3:7])([CH3:6])[CH3:5])([CH3:3])[CH3:2].CS(O)(=O)=O.[O:24]1[CH:29]=[CH:28][CH2:27][CH2:26][CH2:25]1>C(Cl)Cl.C1COCC1>[Si:1]([O:8][C:9]1[CH:10]=[C:11]2[C:15](=[CH:16][CH:17]=1)[N:14]([CH:25]1[CH2:26][CH2:27][CH2:28][CH2:29][O:24]1)[N:13]=[C:12]2[I:18])([C:4]([CH3:7])([CH3:5])[CH3:6])([CH3:3])[CH3:2]

참가 물질

6

반응물 3

HCID 6395Methanesulfonic AcidHCID 80803,4-dihydro-2H-pyranHCID 178455023HCID 178455023, 화합물

생성물 1

HCID 666468565-((tert-Butyldimethylsilyl)oxy)-3-iodo-1-(tetrahydro-2H-pyran-2-yl)-1H-indazole

시약·촉매·용매 2

HCID 6344Dichloromethane용매HCID 8028Tetrahydrofuran용매

실험 절차

Cool a solution of 5-(tert-butyldimethylsilyloxy)-3-iodo-1H-indazole (387.00 g, 1.08 mol) in DCM (2.50 L) and THF (1.00 L) to 10° C. in a 10 L jacketed reactor vessel. To the resulting mixture add methanesulfonic acid (14.0 mL, 216.02 mmol), followed by 3,4-dihydro-2H-pyran (296 mL, 3.24 mol) over 0.5 hours, observing a slight exotherm. Stir the mixture at RT for 3 hours. Cool the reaction to 10° C. and quench with saturated aqueous sodium bicarbonate (2 L). Dilute the mixture with water (2 L) and extract the aqueous layer with DCM (2 L). Wash the combined organic extracts with water (2 L) and brine. Dry the organic mixture over anhydrous sodium sulfate, filter and concentrate in vacuo. Elute the residue through a silica gel pad with eluent (0 to 10% EA/hexanes) to give the title compound. Yield: 150 g (31%). MS (ES) m/z 459 [M+1]+.

후처리

  1. temperatureCool
  2. customthe reaction to 10° C.
  3. customquench with saturated aqueous sodium bicarbonate (2 L)
  4. additionDilute the mixture with water (2 L)
  5. extractionextract the aqueous layer with DCM (2 L)
  6. washWash the combined organic extracts with water (2 L) and brine
  7. dry with materialDry the organic mixture over anhydrous sodium sulfate
  8. filtrationfilter
  9. concentrationconcentrate in vacuo
  10. washElute the residue through a silica gel pad with eluent (0 to 10% EA/hexanes)

출처 및 근거

ORD 기록
ord-b63694b8851b4305b4df9b49ea3df7b7
출처 데이터셋
uspto-grants-2013_09
특허 번호
US08530665B2

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