ChemicalBook CAS DataBase List 2-(4-Chlorophenoxy)phenylacetic acid

2-(4-Chlorophenoxy)phenylacetic acid synthesis

11synthesis methods

Product Name:2-(4-Chlorophenoxy)phenylacetic acid
CAS Number:25563-04-6
Molecular formula:C14H11ClO3
Molecular Weight:262.69

Benzeneacetic acid, 2-(4-chlorophenoxy)-, methyl ester

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25563-04-6
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Yield:25563-04-6 87%

Reaction Conditions:

Stage #1: 2-[(4-chloro-phenoxy)-phenyl]-acetic acid methyl esterwith potassium hydroxide in methanol at 60; for 3 h;
Stage #2: with hydrogenchloride in water; pH=1;

Steps:

9.A

Example 9. Preparation of asenapine via the lactam trans-5-chloro-2,3,3a,12b-tetrahydro-2-methyl-1 H-dibenz [2,3:6,7] oxepino [4,5-c] pyrrol-1-one (VII). A: [2-(4-Chloro-phenoxy)-phenyl-acetic acid (IX) Methyl 2-bromophenylacetate (47.0 grams 216.3 mmol) and 4-chlorophenol (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 1 M 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).

References:

EP1710241,2006,A1 Location in patent:Page/Page column 10

57486-69-8 Synthesis