Patent GB-1145643-A (GB)
Title: Novel 5-‡-h-6-keto-steroids
IPC: C07J9/00
Filed: 1966-08-12
Abstract: 1,145,643. 5α-H-6-kete-steroid. F. HOFFMAN-LA ROCHE & CO. A.G. 12 Aug., 1966 [13 Aug., 1965; 24 March, 1966], No. 40672/68. Divided out of 1,145,641. Heading C2U. The invention comprises novel 5α-H-6-keto steroids of the formula wherein R<SP>1</SP> and R<SP>2</SP> represent a hydroxy or acetoxy group with the proviso that R<SP>1</SP> cannot represent an hydroxy group when R<SP>2</SP> represents an acetoxy group and X represents a grouping of the formulµ in which Y represents a tetrahydropyran-2- yloxy group, X being grouping (a), (b), (e) or (f) when R<SP>1</SP> represents an acetoxy group and R<SP>2</SP> represents a hydroxy group, or grouping (b), (c), (d), (e), (f), (g), (h), (i) or (j), when R<SP>1</SP> and R<SP>2</SP> both represent an acetoxy group. 2# - Acetoxy - 3# - hydroxy - cholester - 6- one and 2#,3# - dihydroxy - cholester - 6 - one can be prepared by treating #<SP>2</SP>-cholester-6-one with silver acetate in the presence of glacial acetic acid and iodine and treating the resulting 2# - acetoxy - 3# - hydroxy - cholestan - 6 - one with potassium carbonate. 2# - Acetoxy - 3# - hydroxy - #<SP>7</SP> - cholester - 6- one and 2#,3#-dihydroxy-#<SP>7</SP>-choleste-6-one are prepared by heating 3#-tosyloxy-#<SP>7</SP>-cholester-6- one with lithium bromide and lithium carbonate, treating the resulting #<SP>2</SP>'<SP>7</SP>-cholestadien-6-one with silver acetate and iodine and then treating the 2# - acetoxy - 3# - hydroxy - #<SP>7</SP> - cholester- 6-one with potassium carbonate. 2#,3# - Diacetoxy - #<SP>7</SP> - 5α - pregnen - 6 - one 20-carboxylic acid methyl ester is prepared by heating 2#,3# - diacetoxy - 7α - bromo - 5α- pregnan-6-one 20-carboxylic acid methyl ester with lithium carbonate and lithium bromide. 2# - Acetoxy - 3# - hydroxy - #<SP>7</SP>'<SP>22</SP> - 5α - ergostadien - 6 - one is prepared by heating 3#- tosyloxy #<SP>7,22</SP> - 5α - ergostadien - 6 - one with N,N-dimethyl aniline and treating the resulting #<SP>2,7</SP>'<SP>22</SP> - 5α -ergostadien - 6 - one with silver acetate and iodine. The 2#- acetoxy - 3# - hydroxy - #<SP>7</SP>'<SP>22</SP> - 5α - ergostadien- 6-one can be acylated by treatment with acetic anhydride in the presence of pyridine to yield the novel 2#,3#,diacetoxy - #<SP>7</SP>'<SP>22</SP> - 5α - ergostadien- 6-one which can be converted into the novel 2#,3# - diacetoxy - 14α - hydroxy - #<SP>7</SP>'<SP>22</SP> - 5α- ergostadien-6-one with selenium dioxide. The 2#,3#- diacetoxy - #<SP>7</SP>'<SP>22</SP> - 5α - ergostadien - 6- one can be treated with ozone and trimethoxyphosphine and the product decomposed with water to yield the novel (20S)-2#,3#-diacetoxy- 20 - formyl - #<SP>7</SP> - 5α - pregnen - 6 - one which can be reacted with 2-methyl-3-butyne-2-ol tetrahydro-pyranyl ether by means of a Grignard reaction to yield after decomposition, novel (22R) - 2#,3# - diacetoxy - 22 - hydroxy- 25 - [tetrahydropyran - (2) - yloxy] - #<SP>7</SP>- cholester-23-yne-6-one. This can be catalytically hydrogenated in presence of platinum catalyst to yield novel (22R)-2#,3#-diacetoxy-22-hydroxy - 25 - [tetrahydropyran - (2) - yloxy]- #<SP>7</SP>-cholester-6-one which can be treated with selenium dioxide to yield (22R)-2#,3#-diacetoxy- 14α,22 - dihydroxy - 25 - [tetrahydropyran - (2)- yloxy] - #<SP>7</SP> - cholester - 6 - one. 2#,3# - Diacetoxy - #<SP>7</SP> - cholester - 6 - one and 2#,3# - diacetoxy - 14α - hydroxy - #<SP>7</SP>- cholester-6-one can be prepared by acylating 2# - acetoxy - 3# - hydroxy - #<SP>7</SP> - cholester - 6- one with acetic anhydride in the presence of pyridine to yield 2#,3# - diacetoxy - #<SP>7</SP> - cholester - 6 - one which can then be treated with selenium dioxide to yield 2#,3#-diacetoxy- 14α-hydroxy-#<SP>7</SP>-cholester-6-one. 2#,3# - Dihydroxy - 20 - hydroxymethyl- #<SP>7</SP> - 5α - pregnen - 6 - one, 2,3,22 - triacetate and 2#,3#,14α - trihydroxy - 20 - hydroxymethyl - #<SP>7</SP> - 5α - pregnen - 6 - one 2,3,22 - triacetate can be prepared by debrominating 2#,3# - dihydroxy - 7α - bromo - 20 - hydroxymethyl - 5α - pregnan - 6 - one 2,3,22 - triacetate with lithium carbonate and lithium bromide to yield 2#,3#-dihydroxy-20-hydroxymethyl - #<SP>7</SP> - 5α - pregnen - 6 - one, 2,3,22- triacetate which can be subjected to allyl oxidation using selenium dioxide to give 2#,3#, 14α - trihydroxy - 20 - hydroxymethyl - #<SP>7</SP> - 5α- pregnen-6-one 2,3,22-triacetate.