NOUVEAUX DERIVES ANTIHISTAMINIQUES DE LA CLASSE DES PHENOXY-AMINES SUBSTITUEES EN ORTHO

1283451 o-Vinylphenol ethers PFIZER Ltd 19 April 1971 [13 March 1970] 12111/70 Heading C2C Novel o-vinylphenol ethers of the general formula wherein R1 is a saturated aliphatic or alicyclic hydrocarbon radical containing at least 5 carbon atoms, Y is either (A) a -Alk-NR2R3 group, in which R2 and R3 are each a C 1-4 alkyl group or NR2R3 is a saturated heterocyclic group and Alk is a divalent saturated aliphatic hydrocarbon group containing 2-4 carbon atoms, the free valencies being located on different carbon atoms, or (B) a group of the formula in which n is 0-3 and Z is a divalent group which completes a saturated heterocyclic ring containing at least one nitrogen atom and at least 4 carbon atoms, any such nitrogen atom being separated from the oxygen atom to which Y is attached by a chain of 2-4 carbon atoms, and R4 is a hydrogen or halogen atom or a C 1-4 alkyl or alkoxy group, and their pharmaceutically-acceptable acid addition salts are prepared (a) by reaction of an alkali metal salt of an o-vinylphenol of the general formula with a halide of the general formula wherein hal is a halogen atom; (b) when Y is a -Alk-NR2R3 group, by reaction of an o-vinylphenol haloalkyl ether of the general formula with an amine of the general formula HNR2R3; (c) by dehydration of an o-(1-hydroxy-ethyl)- phenol ether of the general formula or dehydrohalogenation of the corresponding o-(1-haloethyl)-phenol ether; and (d) when R4 is a hydrogen atom or an alkyl or alkoxy group, by dehydration of an o-(2-hydroxyethyl)-phenol ether of the general formula or dehydrohalogenation of the corresponding o-(2-haloethyl)-phenol ether; followed optionally by salification of the product. o-(1-Hydroxyethyl)-phenol ethers of the seventh general formula above are prepared (a) by reaction of a salicylaldehyde of the general formula with magnesium or lithium and a halide of the general formula hal-CH 2 -R1 or (b) by reduction of an o-acylphenol ether of the general formula (which is prepared, when Y is (A), by reaction of a 4-R4-phenol and a carboxylic acid of the general formula R1CH 2 COOH in the presence of a Lewis acid and (i) reaction of the resulting o-acylphenol of the general formula with a halide of the general formula hal-Alk-Q, wherein Q is an arylsulphonyloxy group, and reaction of the resulting o-acylphenol hal-Alk ether with an amine of the fifth general formula above or (ii) reaction of said o-acylphenol with an alkali metal compound and a halide of the third general formul