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

HRID 2173974Notes

Reaction equation

HRID 2173974 reaction equation
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

Participants

8

Reactant 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

Product 1

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

Reagents, catalysts & solvents 3

HCID 167845palladium(II) acetateCatalystHCID 1140TolueneSolventHCID 6344DichloromethaneSolvent

Conditions

Temperature
90 °C

Procedure

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).

Workup

  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)

Sources & evidence

ORD record
ord-d0e63755bfa44532be0e433eb8917cf9
Source dataset
uspto-grants-2015_06
Patent number
US09056874B2

Reaction notes

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