HALOCYCLOPROPYL SUBSTITUTED PHENOXYALKANOIC ACIDS AND ESTERS

1385828 Phenoxyacetic acid and cyclopropa- [a]naphthoxyacetic acid derivatives STERLING DRUG Inc 13 Aug 1973 [29 Aug 1972] 38311/73 Heading C2C Novel compounds of the Formula I wherein R is hydrogen or C 1-6 alkyl; A and A1 are C 1-3 alkyl; Q is hydrogen, halogen or C 1-3 alkyl; R1 is hydrogen, C 1-3 alkyl or phenyl; R2 is hydrogen or halogen; R2' is hydrogen or halogen, at least one of R2 and R2' being halogen; R3 is hydrogen, C 1-3 alkyl or phenyl; R3' is hydrogen or C 1-3 alkyl; n is 0 or 1 or a compound I where Q and R3 together form an ethylene bridge and (CH 2 ) n is a direct bond to the benzene ring ortho to Q and salts of the free acid may be prepared by (1) reacting a compound of the Formula IV: with a mixture of chloroform, a ketone ACOA1 and an alkali metal hydroxide; (2) reacting a compound IV with a compound of the formula (A)(A1)C(Br)CO 2 R, BrCH 2 CN or BrCH 2 COOR in the presence of base and when the latter two compounds are used, dialkylating the product with A-iodide in the presence of base and, if necessary, hydrolysing the cyano group to a carboxy group; (3) reacting a compound of the Formulµ X, Xa or Xb: with a medium generating a carbene of the formula : CR2R2' and in the case of Xa and Xb thereafter dialkylating and, if necessary, hydrolysing the product as described in (2); (4) for producing the compound Ic, reacting a compound of the formula Xc with a medium generating a carbene : CR3R3'; (5) for producing 2-[p-(2,2-dichlorocyclopropyl)- phenoxy]-2-methylpropionic acid, subjecting p-(2,2-dichlorocyclopropyl)aniline to diazotization and hydrolysis to yield p-(2,2-dichlorocyclopropyl)phenyl, treating the latter compound as in (1) or (2) using acetone or (CH 3 ) 2 C(Br)COOR respectively; followed optionally by esterifying the free acid, hydrolysing an ester to the free acid and/or forming salts of the free acid. The intermediates of the Formula IV may be prepared by ether cleavage of the corresponding anisole which in turn is prepared by reacting a corresponding alkenyl substituted anisole with a medium generating a carbene of the formula : CR2R2'. The intermediates of the Formula X in which R 1 is H may be prepared by reacting a phenol VII as in process (1) or (2) to form an intermediate VIII which on treatment with sodium borohydride yields a compound of the Formula IX in which R 1 is hydrogen, which on dehydration yields X in which R 1 is hydrogen. Alternatively the intermediate X may be prepared by reacting a phenol XI by the proc