Patent GB-1251521-A (GB)
IPC: C07F9/535
Filed: 1968-11-26
Abstract: 1,251,521. Preparation of unsaturated cyclic ketones. SYNTEX CORP. 26 Nov., 1968 [4 Dec., 1967; 25 July, 1968; 4 Nov., 1968], No.56057/68. Headings C2C, C2P and C2U. Enol lactones, i.e. unsaturated lactones having α,#-ethylenic unsaturation with respect to the ring oxygen atom, having at least 5 ring members are reacted with about equimolar quantities of compounds (A) or (B) below in an inert solvent under anhydrous conditions, whereby the ring oxygen atom is replaced by =CH- or =CR<SP>1</SP>- respectively and an α,#- unsaturated carbocyclic ketone is prepared. (where each R is a substituted or unsubstituted, saturated or unsaturated, aliphatic, carbocyclic, carbo-cyclic aliphatic or heterocyclic radical or a C 1-6  alkoxy group and R<SP>1</SP> has any of these values except alkoxy). Preferred enol lactones have the formulµ (wherein R<SP>4</SP> is C 1-6  alkyl; R<SP>6</SP> is oxo, C 2-6  alkylenedioxy or H(#-OH) or an ether or ester thereof; R<SP>2</SP> is H or C 1-6  alkoxy; R<SP>3</SP> and R<SP>4</SP> are C 1-6  alkyl; R<SP>5</SP> is H or CH 3 ; and Z is a carboncarbon single or double bond), but others, including monocyclic compounds, may also be used. Phosphonium ylids of the formulae (A) and (B) above are prepared from the corresponding tetrasubstituted phosphonium halides (from tert.- phosphines and organic halides) with reagents, e.g. bases, capable of removing hydrogen halide. The preparation of the following starting materials, and products derived from the initial products of the process of the invention, is described: 3 - methoxy - estra - 1,3,5(10),8,14- pentaen-17-one (formed together with the corresponding 14#-estra-1,3,5(10),8,15-pentaene in the process of the invention), 3-methoxyestra - 1,3,5(10),8 - tetraen - 17 - one, 1 - bromo- 4-chloropent-3-ene, the compound of the formula 1 - chloropentan - 4 - ol, 4 - (tetrahydropyran-2<SP>1</SP>- yloxy)-1-chloropentane, 4-piperidyl-1-acetoxypent - 3 - ene, 1 - acetoxy - 3 - methylpentan-4- one and the corresponding ethylene ketal, the ethyleneketal of 1-bromo-3-methyl-pentan-4- one, compounds (2), (3), (4), (5) and (6) in the following reaction sequence 2 - methyl - 2 - (# - carbomethoxyethyl) - cyclopentane-1,3-dione, the corresponding 1-ol and its benzoate, l-benzoyloxy-2-methyl-2-(#-carboxyethyl) - 3 - keto - cyclopentane, the enol lactone of the formula where Bz is benzoyl, 3-methoxyestra-1,3,5(10), 8,14 - pentaen - 17# - ol 17 - benzoate, 3 - (nmethoxyphenyl) - propionic acid, 3 - (m-methoxyphenyl) - propanol, 3 - (n - methoxyphenyl)- propyi bromide, compounds of the formulµ (8), (9) and (10) in the following reaction sequence (where R<SP>2</SP> is H or C 1-6  alkyl, R<SP>3</SP> is C 1-6  alkyl, R<SP>8</SP> is H or CH 3  and X is Cl, Br or I), compounds of the formula #,#-dimethoxyethylmalonic acid diethyl ester, γ-dimethoxy butyric acid methyl ester, 4,4- dimethoxybutanol, 17# - hydroxyandrost-4-en- 3-one, compounds of the formulµ (I<SP>1</SP>) to (VI<SP>1</SP>) inclusive (XXXI) and (XXXII) in the following reaction sequences (where R<SP>1</SP> is t.-butyl and R<SP>4</SP> is C 1-6  alkyl), the compound of the formula the corresponding free ol and its tosylate, the compound of the formula and the tosylate of the corresponding compound where OH replaces Br, the corresponding compound where OH replaces Br, the t.-butyl ether of 1-chloro-pentan-4-ol, the compound of the formula the corresponding free omega-ol and its tosylate, the tosylate of the compound of the formula the tosylate of 2-methoxy-2-(3-hydroxypropyl)- 5-methyltetrahydropyran, the corresponding 3-bromopropyl compound, the ethylene ketal of ethyl 3-bromopropyl ketone and the compounds of the formulµ (where x is Br).