4-Chloro-1-methyl-1H-indole synthesis

4synthesis methods

Product Name:4-Chloro-1-methyl-1H-indole
CAS Number:77801-91-3
Molecular formula:C9H8ClN
Molecular Weight:165.62

74-88-4
348 suppliers
$15.00/10g

77801-91-3
13 suppliers
inquiry

Yield: 72%

Reaction Conditions:

Stage #1:4-chloro-1H-indole with sodium hydride in N,N-dimethyl-formamide at 20; for 4 h;
Stage #2:methyl iodide in N,N-dimethyl-formamide at 20; for 15 h;

Steps:

5.A
an oven dried, nitrogen purged, 3 neck, 50 mL round bottom flask, 0.794 mL (6.60 mmol) of 4-chloroindole in 10 mL of dry dimethylformamide is reacted with 0.26Og (6.60 mmol) of 60% sodium hydride dispersed in mineral oil at room temperature for 4 h. 0.411 mL (6.60 mmol) of iodomethane is added and the reaction is allowed to stir at room temperature 15 h. TLC (2:1 hexanes:ethyl acetate) indicates the starting material is gone and new less polar spot. The reaction is quenched with 50 mL of water, extracted 3X50 mL of ethyl acetate, dried (MgSO₄), and concentrated. The crude product is purified by chromatography using hexanes:ethyl acetate as a solvent system to obtain 0.785g of the title compound, 72% yield. MS, ES = 166.1 (M+l); ¹H NMR (DMSO-d6) δ 7.431-7.413 (m, 2H); 7.145-7.064 (m, 2H); 6.442-6.432 (m, IH); 3.795 (s, 3H) ppm.

References:

ELI LILLY AND COMPANY WO2006/107784, 2006, A1 Location in patent:Page/Page column 40