Yield:2002-75-7 85%

Reaction Conditions:

Stage #1: 1-fluoro-4-methoxybenzene;chloroacetyl chloridewith aluminum (III) chloride in dichloromethane at 20 - 38; for 72 h;Heating / reflux;Friedel-Crafts reaction;
Stage #2: with water at 0; for 0.666667 h;

Steps:

1 Example 1; 2-chloro-1-(5-fluoro-2-hydroxy-phenyl)-ethanone

146,7 g (1,1 moles) of anhydrous aluminium chloride is added during 30 min. into a solution of 124,2g (87,5 ml, 1, 1 moles) of chloroacetyl chloride and 126,1 g (114,6 ml, 1,0 moles) of 4-fluoro- anisole in 750 ml dichloromethane. Aluminium chloride is dissolved and the temperature of the reaction mixture is increased from 24°C to 38°C (during the developing of gas, the solvent is gently refluxed). The yellowish-brown solution is stirred at room temperature for 72 hours, then it is poured onto a mixture 1500g of cracked ice and 250ML of water during 40 minutes under vigorous stirring. The icy solution is stirred until all of ice is melted, then layers are separated. The layer containing water is washed with 2X100 ml of dichloromethane, the collected organic layer is washed with 2X100 ml of water. The dichloromethane layer is dried over sodium sulphate, filtered, and the solvent is evaporated. 130 g of cyclohexane is added to the 188 g yellowish oily product. The product is crystallised, filtered and washed with cyclohexane. Thus 152 g (80,5%) yellow powder is obtained. Additional 8,4g (4, 5%) product is prepared by partial evaporation of the filtrate. Thus the total yield is 85%. The crude product is ready to use in the subsequent reaction. The crude product can be purified by under reduced pressure (at 0,1 torr), thus 131 g of pure product can be crystallised from cyclohexane after distillation of 150 g of the crude product described above. The melting point of pure product is: 55, 6-58°C. (This product is characterised only in the J. Indian Chem. Soc. 37,687 (1960) as an oil with 177°C/10 torr boiling point.)

References:

WO2004/41805,2004,A1 Location in patent:Page 42