4-Methylpentyn-3-ol → 1-(5-(((tert-butyldiphenylsilyl)oxy)methyl)-1,6-bis(methylsulfonyl)-1H-indol-2-yl)-2-methylpropan-1-ol

HRID 1051831

반응식

HRID 1051831 반응식
[Si:1]([O:18][CH2:19][C:20]1[C:25]([S:26]([CH3:29])(=[O:28])=[O:27])=[CH:24][C:23]([NH:30][S:31]([CH3:34])(=[O:33])=[O:32])=[C:22](I)[CH:21]=1)([C:14]([CH3:17])([CH3:16])[CH3:15])([C:8]1[CH:13]=[CH:12][CH:11]=[CH:10][CH:9]=1)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.[CH3:36][CH:37]([CH3:42])[CH:38]([OH:41])[C:39]#[CH:40]>C1COCC1.CCN(CC)CC.CCOC(C)=O.Cl[Pd](Cl)([P](C1C=CC=CC=1)(C1C=CC=CC=1)C1C=CC=CC=1)[P](C1C=CC=CC=1)(C1C=CC=CC=1)C1C=CC=CC=1.[Cu]I>[Si:1]([O:18][CH2:19][C:20]1[CH:21]=[C:22]2[C:23](=[CH:24][C:25]=1[S:26]([CH3:29])(=[O:28])=[O:27])[N:30]([S:31]([CH3:34])(=[O:33])=[O:32])[C:39]([CH:38]([OH:41])[CH:37]([CH3:42])[CH3:36])=[CH:40]2)([C:14]([CH3:17])([CH3:16])[CH3:15])([C:8]1[CH:13]=[CH:12][CH:11]=[CH:10][CH:9]=1)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1

참가 물질

8

반응물 2

HCID 982794-Methylpentyn-3-olHCID 89814617N-(4-(((tert-butyldiphenylsilyl)oxy)methyl)-2-iodo-5-(methylsulfonyl)phenyl)methanesulfonamide

생성물 1

HCID 898159981-(5-(((tert-butyldiphenylsilyl)oxy)methyl)-1,6-bis(methylsulfonyl)-1H-indol-2-yl)-2-methylpropan-1-ol수율 90%

시약·촉매·용매 5

HCID 24350Copper(1+) iodide; Copper(I) iodide; Cuprous iodide; Cuprous iodide (CuI)촉매HCID 178418476HCID 178418476, 화합물촉매HCID 8028Tetrahydrofuran용매HCID 8471Triethylamine용매HCID 8857Ethyl Acetate용매

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온도
65 °C

실험 절차

PdCl2(PPh3)2 (277 mg, 0.38 mmol) and CuI (73 mg, 0.38 mmol) were added to a solution of N-(4-(((tert-butyldiphenylsilyl)oxy)methyl)-2-iodo-5-(methylsulfonyl)phenyl)methanesulfonamide (2.45 g, 3.8 mmol) in THF (20 mL) and Et3N (10 mL). The mixture was purged with nitrogen for 10 min followed by addition of 4-methylpent-1-yn-3-ol (745 mg, 7.6 mmol) and stirred at 65° C. for 8 h. The reaction mixture was diluted with EtOAc (50 mL) and washed with 1N HCl (50 mL). The organic layer was separated, and the aq layer was extracted with EtOAc (3×50 mL). The combined organic solution was washed with brine, dried over anhydrous sodium sulfate, filtered and concentrated under reduced pressure. The residue was purified by flash chromatography over silica gel eluting with EtOAc/hexanes (3/7) to provide 1-(5-(((tert-butyldiphenylsilyl)oxy)methyl)-1,6-bis(methylsulfonyl)-1H-indol-2-yl)-2-methylpropan-1-ol (2.1 g, 90% yield). LC-MS m/z 614 [M+H]+. 1H NMR (400 MHz, CDCl3): δ 8.68 (s, 1H), 7.90 (s, 1H), 7.71-7.67 (s, 4H), 7.46-7.35 (m, 6H), 6.77 (s, 1H), 5.21 (d, J=3.2 Hz, 2H), 6.94 (t, J=6.8 Hz, 1H), 3.22 (s, 3H), 2.90 (s, 3H), 2.61 (d, J=6.8 Hz, 1H), 2.37-2.32 (m, 1H), 1.12 (s, 9H), 1.05 (d, J=6.8 Hz, 3H), 1.03 (d, J=6.8 Hz, 3H). 13C NMR (100 MHz, CDCl3): δ 147.25, 135.54, 135.28, 135.00, 133.66, 133.00, 132.89, 129.96, 127.85, 121.68, 115.96, 108.69, 72.30, 62.98, 44.33, 41.59, 32.88, 26.89, 20.23, 19.30, 17.61.

후처리

  1. customThe mixture was purged with nitrogen for 10 min
  2. washwashed with 1N HCl (50 mL)
  3. customThe organic layer was separated
  4. extractionthe aq layer was extracted with EtOAc (3×50 mL)
  5. washThe combined organic solution was washed with brine
  6. dry with materialdried over anhydrous sodium sulfate
  7. filtrationfiltered
  8. concentrationconcentrated under reduced pressure
  9. customThe residue was purified by flash chromatography over silica gel eluting with EtOAc/hexanes (3/7)

출처 및 근거

ORD 기록
ord-7b63f60ff4194c1d9ddf31b360b6393d
출처 데이터셋
uspto-grants-2016_07
특허 번호
US09388190B2

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