Tetrahydrofuran → (+/-)-5-Isobutyl-7-methyl-4-(((tetrahydro-2H-pyran-2-yl)oxy)methyl)-1-tosyl-1H-indole

HRID 2173973Notes

Reaction equation

HRID 2173973 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.C1COCC1.[Br-].[CH2:36]([Zn+])[CH:37]([CH3:39])[CH3:38]>O.CCOC(C)=O>[CH2:36]([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)[CH:37]([CH3:39])[CH3:38]

Participants

6

Reactant 3

HCID 8028TetrahydrofuranHCID 867015385-chloro-7-methyl-4-(((tetrahydro-2H-pyran-2-yl)oxy)methyl)-1-tosyl-1H-indoleHCID 178448254HCID 178448254, compound

Product 1

HCID 86701541(+/-)-5-Isobutyl-7-methyl-4-(((tetrahydro-2H-pyran-2-yl)oxy)methyl)-1-tosyl-1H-indole

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 8857Ethyl AcetateSolvent

Conditions

Temperature
70 °C

Procedure

To a solution of (±)-5-chloro-7-methyl-4-(((tetrahydro-2H-pyran-2-yl)oxy)methyl)-1-tosyl-1H-indole (Example 47-D) (2.7 g, 6.2 mmol) in isobutylzinc(II) bromide in THF (0.5 M, 24.9 mL, 12.4 mmol) was added Pd[(t-Bu)3P]2 (0.5 g, 0.98 mmol), and then the mixture was stirred at 70° C. for 14 h. The mixture was then stirred under reflux for 7 h. The reaction was then diluted with H2O and EtOAc. The mixture was then filtered through a Celite® pad. The filtrate was partitioned. The organic phase was washed with H2O, and brine, dried over Na2SO4, filtered and concentrated. The resulting residue was purified by SiO2 column chromatography (heptane/EtOAc=88/12) to afford the title compound. 1H NMR (400 MHz, ACETONITRILE-d3) δ 7.74 (d, J=3.79 Hz, 1H), 7.58 (d, J=8.59 Hz, 2H), 7.31 (d, J=8.60 Hz, 2H), 6.86-6.94 (m, 2H), 4.90 (d, J=11.12 Hz, 1H), 4.64 (d, J=11.12 Hz, 1H), 4.60-4.64 (m, 1H), 3.81-3.91 (m, 1H), 3.45-3.54 (m, 1H), 2.57 (d, J=7.33 Hz, 2H), 2.52 (s, 3H), 2.35 (s, 3H), 1.79-1.88 (m, 1H), 1.56-1.75 (m, 2H), 1.39-1.55 (m, 4H), 0.84-0.89 (m, 6H).

Workup

  1. stirringThe mixture was then stirred
  2. temperatureunder reflux for 7 h
  3. filtrationThe mixture was then filtered through a Celite® pad
  4. customThe filtrate was partitioned
  5. washThe organic phase was washed with H2O, and brine
  6. dry with materialdried over Na2SO4
  7. filtrationfiltered
  8. concentrationconcentrated
  9. customThe resulting residue was purified by SiO2 column chromatography (heptane/EtOAc=88/12)

Sources & evidence

ORD record
ord-e59d4eb4fad64ef49dec9ffe38547ec9
Source dataset
uspto-grants-2015_06
Patent number
US09056874B2

Reaction notes

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