Hydrochloric Acid → HCID 67333310, compound

Participants

Reaction Conditions

Reaction Steps

Methyl 2-bromophenylacetate (47.0 grams 216.3 mmol) and 4-chloro-phenol (27.8 grams, 215.8 mmol) were dissolved in dioxane (790 ml) while warming to 50° C. To the resulting solution were added, under stirring in an inert nitrogen atmosphere, cesium carbonate (141 grams, 432.2 mmol) and copper(I) chloride (18.56 g, 86.2 mmol). Finally, N,N-dimethylglycine (4.46 grams, 43.2 mmol) was added to the green suspension. The reaction mixture was heated at 110° C. (reflux temperature) for 4 days while stirring. The reaction mixture was filtered over dicalite, which was washed with dioxane (40 ml). The dioxane was removed in vacuo to leave a brownish oil. Ethyl acetate (100 ml) was added to the oil and the pH of the resulting mixture was adjusted to 1 by addition of 1 M HCl (300 ml). The organic phase was washed with saturated brine (300 ml), dried on magnesium sulphate and then concentrated under vacuum to yield 57.2 grams (206 mmol; 95%) of [2-(4-chloro-phenoxy)-phenyl]-acetic acid methyl ester as a brown oil. The oil was dissolved in methanol (250 ml), whereupon KOH (16.2 grams; 1.4 eq) was added. The resulting solution was heated for 3 h at 60° C. The reaction mixture was cooled and the methanol (200 ml) was removed under vacuum. To the residue water (100 ml) was added and the pH was adjusted to 1 by addition of 1M HCl (25 ml). The resulting crystals were filtered off and dried in vacuum at 40° C. to yield 47.3 grams (180 mmol; 87%) of [2-(4-chloro-phenoxy)-phenyl]-acetic acid (IX).

Provenance & Evidence