methyl 2-(4-chlorophenyl)-2-oxoacetate synthesis

11synthesis methods

Product Name:methyl 2-(4-chlorophenyl)-2-oxoacetate
CAS Number:37542-28-2
Molecular formula:C9H7ClO3
Molecular Weight:198.6

5781-53-3 Synthesis

5781-53-3
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108-90-7
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37542-28-2
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$19.00/250mg

Yield:37542-28-2 99 g

Reaction Conditions:

Stage #1: monomethyl oxalyl chloridewith aluminum (III) chloride in chloroform at 0; for 1 h;Inert atmosphere;Friedel-Crafts acylation;
Stage #2: chlorobenzene in chloroform at 0 - 20;Inert atmosphere;Friedel-Crafts acylation;

Steps:

4.1.6. 4-Chloro-phenylglyoxylic acid (14)

Methyl oxalyl chloride (265 g, 2.16 mol) was slowly added to a suspension of aluminium chloride (200 g, 1.5 mol) in 750 ml of chloroform at 0 °C. The reaction mixture was stirred for 1 h at 0 °C, then chlorobenzene (245 g, 2.19 mol) was slowly added at this temperature. The resulting mixture was stirred for 16 h at room temperature, then poured on water and diluted with dichloromethane. The phases were separated, the organic layer was washed with water, dried over sodium sulfate and evaporated. The remainder was purified by chromatography on silica gel, using ethyl acetate/heptane 1:9 as eluent, delivering methyl 4-chloro-phenylglyoxylate (99 g, 0.5 mol). This intermediate was dissolved in 800 ml of dioxane and 800 ml of 1 N sodium hydroxide were added. The mixture was stirred for 2 h at room temperature, then acidified to pH 1 with 2 N hydrochloric acid and extracted with ethyl acetate. The organic layer was washed with brine, dried over sodium sulfate and evaporated to deliver 4-chloro-phenylglyoxylic acid (14, 86 g, 0.47 mol 21%). ¹H NMR (CDCl₃): δ = 7.53 (d, 2H), 8.10 (br s, 1H), 8.32 (d, 2H). MS (ESI): m/z = 186 (M+1), 165 (M-OH).

References:

Lamberth, Clemens;Trah, Stephan;Wendeborn, Sebastian;Dumeunier, Raphael;Courbot, Mikael;Godwin, Jeremy;Schneiter, Peter [Bioorganic and Medicinal Chemistry,2012,vol. 20,# 9,p. 2803 - 2810] Location in patent:experimental part