Iodine → 5,7-Difluoro-6-iodo-1-(triisopropylsilyl)-1H-indole

HRID 923689Notes

Reaction equation

[F:1][C:2]1[CH:3]=[C:4]2[C:8](=[C:9]([F:11])[CH:10]=1)[N:7]([Si:12]([CH:19]([CH3:21])[CH3:20])([CH:16]([CH3:18])[CH3:17])[CH:13]([CH3:15])[CH3:14])[CH:6]=[CH:5]2.CN(C)CCN(C)CCN(C)C.C([Li])(CC)C.[I:39]I>C1COCC1>[F:1][C:2]1[CH:3]=[C:4]2[C:8](=[C:9]([F:11])[C:10]=1[I:39])[N:7]([Si:12]([CH:16]([CH3:18])[CH3:17])([CH:19]([CH3:21])[CH3:20])[CH:13]([CH3:14])[CH3:15])[CH:6]=[CH:5]2

Participants

Conditions

Temperature: -70 °C

Procedure

5,7-difluoro-1-(triisopropylsilyl)-1H-indole (1.4 g, 4.5 mmol) and pentamethyldiethylene-triamine (830 mg, 4.8 mmol) were combined in 10 mL dry THF, cooled to −70° C. and treated in portions with sec-butyl lithium (3.4 mL, 1.4 M, 4.8 mmol) and stirred for 3 h at this temperature. Iodine (1.3 g, 5.0 mmol) in 5 mL THF was added, the mixture was stirred for 50 min, quenched by addition of 3 mL sat. NH4Cl and partitioned between diethyl ether and water. The organic phase was washed with sat. NaCl, dried (Na2SO4), evaporated and purified by flash chromatography (SiO2; hexanes) the title compound as a clear oil which solidified on standing (1.9 g, 90%). 1H NMR (400 MHz, CDCl3) δ 7.34 (d, J=3.1 Hz, 1H), 7.14 (dd, J=7.7, 0.9 Hz, 1H), 6.60 (t, J=3.1 Hz, 1H), 1.67 (m, 3H), 1.13 (d, J=7.6 Hz, 18H). 19F NMR (376 MHz, CDCl3) δ −101.37, −105.33. MP: 74-76° C.

Workup

stirringthe mixture was stirred for 50 min
customquenched by addition of 3 mL sat. NH4Cl
custompartitioned between diethyl ether and water
washThe organic phase was washed with sat. NaCl
dry with materialdried (Na2SO4)
customevaporated
custompurified by flash chromatography (SiO2; hexanes) the title compound as a clear oil which

Sources & evidence

ORD record: ord-aa000446528b4d97b5f9ff077468db7f
Source dataset: uspto-grants-2016_03
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US09278985B2

Reaction notes

Loading…