GB1140322A - Novel indane derivatives, and processes for their preparation - Google Patents

Abstract

1,140,322. 1 - Hydroxy - 4 - carboxyalkyl- 7a - alkylhexahydroindane - 5 - ones and derivatives. ROUSSEL-UCLAF. 18 July, 1967 [27 July, 1966], No. 32984/67. Headings C2C and C2U. The invention comprises compounds of Formulµ (I) (and its salts), (III), (IV), (V), (IX) and (X), wherein Y is alkyl, R<SP>1</SP> is C 1-10 acyl, R is C 1-8 alkyl and X is a ketal residue (e.g. ethylenedioxy); in intermediates (VI) and (VII), R<SP>2</SP> is aryl. In scheme (I), (II) is converted to (III) with BOH+acid, (III) to (IV) with a reactive derivative of the acid R<SP>1</SP>OH, (IV) to (V) with a ketalizing agent + strong acid, (V) to (VI) with R<SP>2</SP>Mg-halide, followed by strong mineral acid hydrolysis, (VI) to (VII) with an esterifying agent, and (VII to (I) with an oxidizing agent followed by aq. alcoholic alkali-metal base. In scheme (II), (VIII) is converted to (IX) with an alkali metal borohydride, (IX) to (X) with H 2 /Pd, followed by esterification, and (X) to (I) with an aq. alcoholic alkali-metal base. Estradiol 3-methyl ether is synthesized as follows: I(Y=Me) is formylated, the formyl derivative is then reacted with p-MeOC 6 H 4 - MgBr to give 1#-hydroxy-4-carboxymethyl-5- p - methoxyphenyl - 7a# - methyl - 3aα,4#,7,7atetrahydroindane (characterized as methyl ester) which is reduced (H 2 /Pd-C) to the hexahydroindane, the latter acetylated and then cyclized with syrupy phosphoric acid to 3- methoxy-6-oxo - 17# - acetoxy - estra - 1,3,5(10)- triene (X1), this being saponified to the 17#- hydroxy compound in which the 6-oxo group is reduced with H 2 /Pt-C. (XI) is characterized as the dinitrophenylhydrazone.