5-Chloro-2-fluorobenzoyl chloride

As monomer, bis[4-fluoro-3-(p-methoxylbenzo-yl)]biphenyl that contains two pendant methox-yphenyl groups is used. It is synthesized by a Friedel-Crafts reaction of 5-chloro-2-fluorobenzoyl chloride with anisole, followed by a nickel-mediated homo-coupling reaction. 

The typical synthesis of the intermediate 245 can be carried out by two routes (i) preparation from 3-chloro-4-fluoroaniline 248 and malonate 249 through the formation of 250 and 251 (Scheme 12.60) (ii) preparation from 2,4-dichloro-5-fluorobenzoyl chloride 252 and enamine 253 or CH2(C02Et)2 (Scheme 12.61). Heravi et al. have prepared 243 through borate complexes after formation of 245. In this method, 245 was converted to borate complex, which was treated with 244 in the presence of triethylamine to afford 243 in high yields (Scheme 12.62). 

Preparation by Friedel-Crafts acylation of p-chloro-phenol with o-fluorobenzoyl chloride in the pres-C1 ence of aluminium chloride at 195° for 25 min (70%) [523]. 

Preparation by partial demethylation of 2-chloro-2 -fluoro-4,6-dimethoxy-benzophenone (SM) in ethylene dichloride in the presence of aluminium chloride at reflux (90°) for 3 h [476]. SM was obtained by reaction of o-fluorobenzoyl chloride with 5-chlororesorcinol dimethyl ether in methylene chloride in the presence of aluminium chloride at r.t. for 4 h [476]. 

A mixture of 6.6 parts of y-chloro-4-fluorobutyrophenone and 12.5 parts of 1-(2-methoxyphenyl)piperazine, heated for 10 hours at a temperature of 110°C. The reaction mixture is treated with 800 parts of ether and filtered. The ether layer is washed with water, dried over anhydrous potassium carbonate and filtered, whereupon hydrogen chloride gas is introduced into the solution. The precipitate is collected on a filter and dissolved in a mixture of 240 parts of 2-propanol and 80 parts of acetone to yield l-[y-(4-fluorobenzoyl)propyl]-4-(2-methoxyphenyl)piperazine hydrochloride. This monohydrochloride is collected on a filter and dissolved in 240 parts of 2-propanol. Anhydrous, gaseous hydrogen chloride is passed through the solution. On cooling, the l-[y-(4-fluorobenzoyl)propyl]-4-(2-methoxyphenyl)piperazine hydrochloride precipitates. 

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