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761402-59-9

METHYL 1-(4-CHLOROBENZYL)-1H-INDOLE-3-CARBOXYLATE synthesis

3synthesis methods
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Yield:761402-59-9 78%

Reaction Conditions:

Stage #1: 3-methoxycarbonylindole in N,N-dimethyl-formamide;mineral oil at 20; for 0.0833333 h;
Stage #2: 4-chlorobenzyl bromide in N,N-dimethyl-formamide;mineral oil at 20; for 0.333333 h;

Steps:

6.6-1 Step 6-1. methyl 1-(4-chlorobenzyl)-1H-indole-3-carboxylate (INT-6A)

A 250 mL round bottom flask containing methyl 1H-indole-3-carboxylate (4.39 g, 1.0 equiv., 37.4 mmol) in DMF (30 mL) was added NaH (60% dispersion in mineral oil, 2.04 g, 1.4 equiv., 51.1 mmol) and then the suspension was stirred at rt for 5 minutes, 10 1-(bromomethyl)-4-chlorobenzene (7.0 g, 1.3 equiv., 34.1 mmol) was slowly added. Stirred at rt for 20 minutes. Monitored by LCMS.20 min: Coupling complete. Quenched with NH4Cl (100 mL) slowly. Product was extracted with EtOAc (300 mL), washed with brine (200 mL), dried over Na2SO4, filtered, and concentrated in vacuo to afford 8.0 g (78% yield) of methyl 1-(4-chlorobenzyl)-1H-indole-3-carboxylate (INT-6A); LCMS 15 (m/z) calculated for C17H14ClNO2: 299.07; found 300.2 [M+H] +, tR = 5.37 min (Method 3).

References:

WO2022/61008,2022,A2 Location in patent:Page/Page column 214-215