Dichloromethane → 1-(4-Fluorobenzyl)-3-(1-methylpiperidin-4-yl)-5-hydroxy-1H-indole

HRID 1766240Notes

Reaction equation

HRID 1766240 reaction equation
[Si]([O:8][C:9]1[CH:10]=[C:11]2[C:15](=[CH:16][CH:17]=1)[NH:14][CH:13]=[C:12]2[CH:18]1[CH2:23][CH2:22][N:21]([CH3:24])[CH2:20][CH2:19]1)(C(C)(C)C)(C)C.[H-].[K+].[F:27][C:28]1[CH:35]=[CH:34][C:31]([CH2:32]Br)=[CH:30][CH:29]=1.ClCCl>CO>[F:27][C:28]1[CH:35]=[CH:34][C:31]([CH2:32][N:14]2[C:15]3[C:11](=[CH:10][C:9]([OH:8])=[CH:17][CH:16]=3)[C:12]([CH:18]3[CH2:19][CH2:20][N:21]([CH3:24])[CH2:22][CH2:23]3)=[CH:13]2)=[CH:30][CH:29]=1

Participants

6

Reactant 4

HCID 6344DichloromethaneHCID 680214-Fluorobenzyl bromideHCID 82127Potassium hydrideHCID 179801335-(t-Butyldimethylsilanyloxy)-3-(1-methylpiperidin-4-yl)-1H-indol

Product 1

HCID 179801041-(4-Fluorobenzyl)-3-(1-methylpiperidin-4-yl)-5-hydroxy-1H-indoleYield 90%

Reagents, catalysts & solvents 1

HCID 887MethanolSolvent

Procedure

By a method similar to Preparation 32, using 5-(t-butyldimethylsilanyloxy)-3-(1-methylpiperidin-4-yl)-1H-indol (400 mg, 1.16 mmol), potassium hydride (139 mg of a 35% dispersion oil, 1.21 mmol) and 4-fluorobenzyl bromide (148 μL, 1.21 mmol), and chromatographic purification with a 9:1 mixture of dichloromethane and methanol provided 353 mg (90%) of the desired compound as an orange foam: 1H NMR (dmso-d6): 8.61 (s, 1H), 7.25-7.00 (m, 6H), 6.82 (d, 1H, J=2.0 Hz), 6.54 (dd, 1H, J=8.8, 1.6 Hz), 5.20 (s, 2H), 2.84 (br d, 2H, J=11.6 Hz), 2.62-2.50 (m, 1H), 2.19 (s, 3H), 2.01 (br t, 2H, J=11.0 Hz), 1.85 (br d, 2H, J=13.2 Hz), 1.62 (qd, 2H, J=12.0, 2.4 Hz). MS (APCI): m/e 339.2 (M+1).

Workup

  1. customBy a method similar to Preparation 32

Sources & evidence

ORD record
ord-c375ab38a7bf4587b4d12abfd97bbfbb
Source dataset
uspto-grants-2007_06
Patent number
US07230011B2

Reaction notes

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