Patent GB-929983-A (GB)
Title: 6-formyl steroids
Inventor: KIRK DAVID NEVILLE
IPC: C07J1/00
Filed: 1960-11-07
Abstract: The invention comprises 3-enol-ethers of 6-formyl-3-oxo-D 4-steroids and a process for their preparation which comprises treating a corresponding 3-enol-ether of a 3-oxo-D 4-steroid with the Vilsmeier reagent followed by aqueous hydrolysis.  The products preferably have one of the formulae <FORM:0929983/IV(a)/1> <FORM:0929983/IV(a)/2> (wherein R1 is CHO; R2 is H or CH3; R3 is H2, H(OH) or =O; R4 is H, OH or Oacyl, the acyl group containing at most 10 carbon atoms; R5 is R4 or F; R6 is H, CH3, C2H5, vinyl, ethynyl, propynyl, chlorethynyl or OH; R7 is CH2, CHR4, C=CH2, C=CH.CH3, CH.CH2OH, CHCN or CH.Hal where Hal is Cl, Br or F, or R4 and R7 together form -O.C(CH3)2.O.CH- or -O.CH; R8 is =O, H(OH) or HO(acyl); or R4 and R6 together can be keto or -O.CO.(CH2)2-; and R is O-alkyl, O-hydroxyalkyl, O-cycloalkyl or O-aralkyl) or the corresponding 9(11)-dehydro compounds.  The Vilsmeier reagent is preferably a complex formed from a formamide, e.g. dimethyl formamide, and an acidic reagent, such as phosphorus oxychloride or phosgene.  The present products, on prolonged heating with alcohols R1OH (wherein R1 has a lower molecular weight than R), undergo interchange of R1 for R.  Free hydroxy groups are generally converted to formyloxy groups in the process of the invention, but they can readily be freed by hydrolysis.  16b - Methyl- 16a ,17a - epoxypregnan- 20-ones are converted directly to 6-formyl derivatives of 17a -hydroxy-16-methylenepregnan-20-ones by using 2 moles of reagent, and 16a ,17a -epoxy-pregnan-20-ones yield 16b -halo-17a -hydroxypregnan-20-ones.  Examples describe the preparation of many 6-formyl steroids of the above general formulae (including 19-nor and D 9(11)-analogues) and also of some 17a ,20:20,21-bismethylenedioxy- 3-alkoxy-6-formylpregna-3, 5-dienes; 3-ethoxy-6-formly- 25D-spirosta-3,5-diene; 6-formyl-3-methoxy- 16-methylpregna-3,5,16-triene-20-one; the 3-enol-ether of 6-formylpregna- 4,17(20)-dien- 3-one- 21-oate ethylester; 3-methoxy-6- formyl-17a ,21-methoxymethylenedioxypregna- 3, 5-diene- 11,20-dione; 6-formyl-20-hydroxy-3-methoxypregna-3,5-diene-18-oic acid (18-->20) lactone; 21-benzylidene- 3-ethoxy- 6-formyl- 16a , 17a -isopropylidenedioxypregna- 3,5-dien- 20-one; 6-formyl- 3-methoxy- 16a ,17a -cyclomethylenepregna-3, 5-diene-20-one; 6-formyltestololactone 3-enol methyl ether; 6-formylcortisone 17,21-acetonide 3-enol methyl ether; 21-acetoxy- 6-formyl- 3-methoxypregna- 3,5,17 (20)-trien- 11-one; 15a -acetoxy- 6-formyl-3-methoxypregna-3,5-diene-20-one; 21-acetoxy-9a -fluoro- 6-formyl- 11b , 17a - dihydroxy-3-methoxy-pregna-3,5-diene-20-one; and 6-formyl-3-methoxy- 9b ,10a -pregna- 3,5-diene-20-one.  Reference is also made in general to the use of steroids of the androstane, 19-norandrostane, 9b ,10a -androstane, cholestane, spirostane, ergostane, stigmastane, pregnane, 19-norpregnane and 9b ,10a -pregnane series containing hydroxyl, thiol, carbonyl, carbalkoxy, cyano, alkyl, alkenyl, alkynyl, methylene, ethylidene, benzylidene, lactone, ether, ketal, spiroketal, halogen, ketol and epoxy groups, protected corticoid side chains and unsaturated linkages at most of the positions in the steroid nucleus and the 17-side chain in the process of the invention.  A list of further starting materials is also provided.  Enol ether starting materials are prepared from the corresponding D 4-3-oxo-steroids by standard procedures.  17b - Propionyloxy- 17a -(prop-11-ynyl)-and-rost-4-en-3-one is prepared from the 17-ol and propionic anhydride.  The corresponding 17a -vinyl compound is prepared similarly.  Specifications 919,565, 920,521 and U.S.A. Specification 2,846,452 are referred to.