Patent GB-1461876-A (GB)
Title: Alpha-1-aralkylaminoalkyl-aralkoxybenzyl alcohols process for their manufacture and pharamaceutical preparations con taining them
IPC: C07C215/58
Filed: 1974-02-05
Abstract: 1461876 α - (1 - Aralkylaminoalkyl) - aralkoxybenzyl alcohols CIBA-GEIGY AG 5 Feb 1974 [7 Feb 1973] 05275/74 Heading C2C Novel α - (1 - aralkylaminoalkyl) - aralkoxybenzyl alcohols of the general formula wherein each of Ar 1 , Ar 2  and Ar 3  is a phenyl group, optionally substituted by at least one substituent selected from halogen atoms and C 1-4  alkyl, C 1-4  alkoxy and trifluoromethyl groups, Ph is a 1,3- or 1,4-phenylene group, optionally substituted by one substituent as indicated above for Ar 1 , n is 0 or 1-4 and each of m and p is 1-4, and acid addition salts thereof are prepared (a) by reducing a carbonyl compound of the general formula wherein either X is O and Y is H 2  or X is H, OH andYis O,and (b) by condensing compounds of the general formulµ Ar 1 -C m H 2  m -T or a reactive salt thereof and U-C p H 2p -CH(Ar 2 - Ar 3 ) or a reactive salt thereof, wherein either T is -O-Ph-CH(OH)-CH(C n H 2n+1 )NH 2  and U is Cl or Br or T is Cl or Br and U is and optionally converting a resulting free compound into a salt or a resulting salt into the free compound or another salt. Ketones of the general formula are prepared by reacting compounds of the general formulae and may optionally be isolated as acid addition salts. Bromides of the general formula are prepared by reacting compounds of the general formulµ and brominating the resulting ether of the general formula Amines of the general formula are prepared by reducing a corresponding imine (prepared by reacting a compound of the general formula with an appropriate aldehyde) and may be isolated as acid addition salts. Ethers of the general formula are prepared by reacting compounds of the general formulµ and may be isolated as acid addition salts. Amides of the general formula are prepared by reacting an amine of the general formula with the appropriate acid chloride or anhydride. γ,γ-Dipheayl-butyryl chloride is prepared by reacting benzophenone with diethyl succinate in the presence of potassium and t-butanol, followed by aqueous HCl, heating the resulting α-benzhydrylidene-succinic acid monoethyl ester with HBr and acetic acid, catalytically hydrogenating the resulting 4,4-diphenyl-3-butenoic acid and treating the resulting 4,4-diphenylbutyric acid with thionyl chloride. 3,3-di-p-Fluorophenylacrolein is prepared by reacting 2,4,4,6 - tetramethyl - 5,6 - dihydro- 1,3-oxazine with n-butyl lithium and 4,41-difluorobenzophenone, reducing the resulting 2- [# - hydroxy - #,# - di - (p - fluorophenyl) ethyl]- 4,4,6 - trimethyl - 5,6 - dihydro - 1,3 - oxazine with sodium borohydride and refluxing the resulting corresponding tetrahydro-1,3-oxazine with aqueous oxalic acid. 3 - Amino - 1,1 - diphenylbutane hydrochloride is prepared by reacting methyl 2,2-diphenylethyl ketone with ammonium carbonate and formic acid, followed by HCl. d - erythro - α - [1 - (3,3 - Diphenylpropylamino)ethyl] - p - (m - chlorobenzyloxy)benzyl acetate hydrochloride is prepared by reacting d - erythro - α - [1 - (3,3 - diphenylpropylamino)- ethyl] - p - (m - chlorobenzyloxy)benzyl alcohol hydrochloride with acetyl chloride. Pharmaceutical compositions having antihypertensive and bradycardic activity comprise, as active ingredient, an α-(1-aralkylaminoalkyl)-aralkoxybenzyl alcohol of the first general formula above or a physiologically tolerable acid addition salt thereof, together with a pharmaceutically suitable carrier.