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

Temperature

70 °C

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).

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)

ORD record

ord-e59d4eb4fad64ef49dec9ffe38547ec9

Source dataset

uspto-grants-2015_06

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US09056874B2