1-Chloro-4-(chloromethyl)benzene → ethyl 1-(4-chlorobenzyl)-7-methyl-1H-indole-2-carboxylate

HRID 83679Notes

Reaction equation

[CH3:1][C:2]1[CH:3]=[CH:4][CH:5]=[C:6]2[C:10]=1[NH:9][C:8]([C:11]([O:13][CH2:14][CH3:15])=[O:12])=[CH:7]2.C(=O)([O-])[O-].[K+].[K+].[Cl:22][C:23]1[CH:30]=[CH:29][C:26]([CH2:27]Cl)=[CH:25][CH:24]=1>CN(C=O)C>[Cl:22][C:23]1[CH:30]=[CH:29][C:26]([CH2:27][N:9]2[C:10]3[C:6](=[CH:5][CH:4]=[CH:3][C:2]=3[CH3:1])[CH:7]=[C:8]2[C:11]([O:13][CH2:14][CH3:15])=[O:12])=[CH:25][CH:24]=1

Participants

Conditions

Temperature: 60 °C

Procedure

ethyl 7-methyl-1H-indole-2-carboxylate (500 mg, 2.46 mmol) was dissolved in DMF (20 mL) and granular potassium carbonate (425 mg, 3.08 mmol) and p-chlorobenzylchloride (0.39 mL, 3.08 mmol) were added The mixture was stirred for 3 d at 60° C., after which time the incomplete reaction was terminated by dilution with ethyl acetate and subsequent washing with brine (3×). The organic phase was dried over magnesium sulfate, concentrated, and purified vial silica gel flash chromatography (80 g silica, 40% EtOAc/hexanes.) The title compound was obtained as white crystals. (Yield: 390 mg, 1.19 mmol, 46%) 1H NMR (400 MHz, CDCl3) 7.56, 7.41, 7.32-6.96, 6.78, 6.08, 4.31-4.25, 2.54, 1.34

Workup

customafter which time the incomplete reaction
customwas terminated by dilution with ethyl acetate
washsubsequent washing with brine (3×)
dry with materialThe organic phase was dried over magnesium sulfate
concentrationconcentrated
custompurified vial silica gel flash chromatography (80 g silica, 40% EtOAc/hexanes.) The title compound
customwas obtained as white crystals

Sources & evidence

ORD record: ord-cf4c02855979495380ce955f30977286
Source dataset: uspto-grants-2014_09
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US08846684B2

Reaction notes

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