Patent GB-1265978-A (GB)
IPC: C07D213/50
Filed: 1969-04-24
Abstract: 1,265,978. Basic ethers. SANDOZ Ltd. 24 April, 1969 [29 April, 1968 (2)], No. 20908/69. Heading C2C. Compounds of the general Formula I (wherein the R 1 's, which may be the same or different, each represent C 1-4  alkyl other than tert.-butyl or together (CH 2 ) 4  or (CH 2 ) 5 ; the R 2 's, which may be the same or different, each represent H or C 1-4  alkyl other than tert. -butyl; Z represents a radical of Formula II:  or a radical of Formula III: in which R 3  = H or a radical of Formula IV: R5=H, 3-pyridyl or a radical of Formula IV and the R 4 's and Y's, which may be the same or different, each represent H, F, Cl, Br, C 1-4  alkyl or alkoxy or Ph, provided that (i) both the R 4 's=H when R 3  or R 5 =H, (ii) not more than one of the and Y's=Ph and (iii) the R 4 's and Y's together represent a total of not more than two alkyl and/or alkoxy substituents), their N-oxides and acid addition salts of the compounds and N-oxides are prepared by (i) catalytically hydrogenating a compound of Formula Va:  (ring A has one or two double bonds or a 1-, 3- or 5-OH group, or such an OH group and one double bond), (ii) dehydrogenating and, if required, dehydrating a compound of Formula Vb: (iii) reacting a compound of Formula VI: (M=alkali metal) with a compound of Formula VII: (Hal=Cl, Br, I; the R<SP>1</SP> 2 's, which may be the same or different, each represent H or C 1-4  alkyl other than tent.-butyl ; the R x 's either both represent H or both represent C 1-4  alkyl other than tert.-butyl, provided that when the R x 's = alkyl both the R<SP>1</SP> 2 <SP>'</SP>s=H), (iv) reducing a compound of Formula VIII: (v) reducing a compound of Formula IX: or (vi) treating a compound of Formula X: (the Y<SP>1</SP>'s and R<SP>1</SP> 4 's are equivalent to Y and R 4  but with the proviso that, when they are not all H, they are such that the ring carrying the Y<SP>1</SP>'s is identical to the ring carrying the R<SP>1</SP> 4 's) with bromine and acetic acid, optionally followed in each case by oxidation and/or salt formation. Starting materials of Formula Va and Vb are prepared by (a) reacting a compound of Formula XI:  (Rg=R 3  or R 5  and one of the two dotted lines = carbon to carbon bond) with a Grignard reagent of Formula XII: and hydrolysing the product, (b) reacting a compound of Formula XIII: (}xy = >C =CH- or >CH-CH 2 -) with a Grignard reagent of Formula XIV: and hydrolysing the product, (c) subjecting a compound of Formula XV: (V=OH, W=H; t, u= single bonds, or W= OH, V=H, one of t, u=single bond and the other=double bond) to acid dehydration conditions, or (d) reducing a compound of Formula XVI: Compounds of Formula XI are prepared by (a) decarboxylating a compound of Formula XVII: (R<SP>1</SP> g  = K g  except that it may only be H when the double bond is adjacent thereto, a single one of the X's = C 2-5  alkoxycarbonyl and a single one of the dotted lines = carbon to carbon bond, the alkoxycarbonyl radical and double bond not being adjacent), or (b) reacting a compound of Formula XVIII: with a compound of Formula VII. Compounds of Formula XVII are prepared by reacting a compound of Formula XIX: (P = -CH = CH.CO- or -CO.CH = CH-; R<SP>11</SP>g=Rg except that it may only be H when it is attached to the -CO.CH=CHP group) with R<SP>1</SP> 6 O.OCCH 2 COCH 3  (R<SP>1</SP> 6  = C 1-4  alkyl) in the presence of a base and an inert organic solvent under substantially anhydrous conditions. Compounds of Formula XIX are prepared by (a) reacting R<SP>111</SP>gCHO (R<SP>111</SP> g  = R g  except that it may not represent H) with a compound of Formula XXII: under Claisen condensation conditions, or (b) reacting R g COCH 3  with a compound of Formula XXIV: under Claisen condensation conditions. Compounds of Formula XVIII are prepared by reacting a compound of Formula XXV: (Q=H or C 1-4  alkyl) with R<SP>111</SP>gCHO under Claisen condensation conditions, reacting the product with R<SP>1</SP> 6 O.OCCH 2 COCH 3  in the presence of a base and an inert organic solvent under substantially anhydrous conditions and decarboxylating the resulting compound. Compounds of Formula VI are prepared by reacting a compound of the Formula XXVIII: with a Grignard reagent of Formula XII, hydrolysing the product and either catalytically hydrogenating or dehydrating and dehydrogenating the resulting compound. Compounds of Formula VIII are prepared from a compound of Formula XXX: (T=H or a non-sterically hindered leaving group) by standard methods. In turn, the compounds of Formula XXX are prepared by reacting a compound of Formula VI with a compound of Formula XXXII: Compounds of Formula X are prepared by reacting a compound of Formula XXXIII: with at least two moles of a methylmagnesium halide and hydrolysing the product. In turn, the compounds of Formula XXXIII are prepared by reacting a compound of Formula XXIV with at least two moles of a compound of Formula XXXV: in the presence of a strong base and an inert organic solvent. The compounds of the invention are hypolipemic agents, and may be administered in the form of pharmaceutical preparations containing them in association with a carrier.