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Water → 7-Methyl-4-(((tetrahydro-2H-pyran-2-yl)oxy)methyl)-1-tosyl-5-vinyl-1H-indole

HRID 2173974
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HRID 2173974 반응식
Cl[C:2]1[C:3]([CH2:22][O:23][CH:24]2[CH2:29][CH2:28][CH2:27][CH2:26][O:25]2)=[C:4]2[C:8](=[C:9]([CH3:11])[CH:10]=1)[N:7]([S:12]([C:15]1[CH:21]=[CH:20][C:18]([CH3:19])=[CH:17][CH:16]=1)(=[O:14])=[O:13])[CH:6]=[CH:5]2.C([O-])([O-])=O.[K+].[K+].O.CO[C:39]1C=CC=C(OC)[C:44]=1C1C=CC=CC=1P(C1CCCCC1)C1CCCCC1>C1(C)C=CC=CC=1.C(Cl)Cl.CC([O-])=O.CC([O-])=O.[Pd+2]>[CH3:11][C:9]1[CH:10]=[C:2]([CH:39]=[CH2:44])[C:3]([CH2:22][O:23][CH:24]2[CH2:29][CH2:28][CH2:27][CH2:26][O:25]2)=[C:4]2[C:8]=1[N:7]([S:12]([C:15]1[CH:21]=[CH:20][C:18]([CH3:19])=[CH:17][CH:16]=1)(=[O:14])=[O:13])[CH:6]=[CH:5]2
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참가 물질

8

반응물 4

HCID 962WaterHCID 11430Potassium CarbonateHCID 112698722-Dicyclohexylphosphino-2',6'-dimethoxybiphenylHCID 867015385-chloro-7-methyl-4-(((tetrahydro-2H-pyran-2-yl)oxy)methyl)-1-tosyl-1H-indole

생성물 1

HCID 867015427-Methyl-4-(((tetrahydro-2H-pyran-2-yl)oxy)methyl)-1-tosyl-5-vinyl-1H-indole

시약·촉매·용매 3

HCID 167845
palladium(II) acetate
촉매
HCID 1140Toluene용매
HCID 6344Dichloromethane용매

반응 조건

온도
90 °C

실험 절차

To a suspension of (±)-5-chloro-7-methyl-4-(((tetrahydro-2H-pyran-2-yl)oxy)methyl)-1-tosyl-1H-indole (Example 47-D) (2.1 g, 4.8 mmol), vinylboronic anhydride pyridine complex (3.5 g, 14.5 mmol) and K2CO3 (6.7 g, 48.4 mmol) in toluene (10 mL)/H2O (4 mL) were added Pd(OAc)2 (0.22 g, 0.97 mmol) and S-Phos (CAS; 657408-07-6) (0.80 g, 1.9 mmol), and then the mixture was stirred at 90° C. under N2 atmosphere for 4 h. The reaction mixture was cooled to room temperature, diluted with CH2Cl2 and partitioned. The organic phase was washed with H2O and brine, dried over Na2SO4, and then filtered. Concentration of the filtrate gave a residue that was purified by SiO2 column chromatography (heptane/EtOAc=95/5 to 7/3) to give the title compound. 1H NMR (400 MHz, ACETONITRILE-d3) δ 7.78 (d, J=3.79 Hz, 1H), 7.58 (d, J=8.59 Hz, 2H), 7.26-7.38 (m, 3H), 7.13 (dd, J=11.12, 17.43 Hz, 1H), 6.95 (d, J=3.79 Hz, 1H), 5.70 (dd, J=1.26, 17.43 Hz, 1H), 5.31 (dd, J=1.26, 11.12 Hz, 1H), 4.93 (d, J=11.37 Hz, 1H), 4.72 (d, J=11.37 Hz, 1H), 4.56-4.66 (m, 1H), 3.78-3.92 (m, 1H), 3.35-3.57 (m, 1H), 2.57 (s, 3H), 2.35 (s, 3H), 1.56-1.75 (m, 2H), 1.38-1.56 (m, 4H).

후처리

  1. temperatureThe reaction mixture was cooled to room temperature
  2. custompartitioned
  3. washThe organic phase was washed with H2O and brine
  4. dry with materialdried over Na2SO4
  5. filtrationfiltered
  6. customConcentration of the filtrate gave a residue that
  7. customwas purified by SiO2 column chromatography (heptane/EtOAc=95/5 to 7/3)

출처 및 근거

ORD 기록
ord-d0e63755bfa44532be0e433eb8917cf9
출처 데이터셋
uspto-grants-2015_06
DOI
10.6084/m9.figshare.5104873.v1
특허 번호
US09056874B2

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