4-Fluoro testosterone

Dehydration to olefins, which sometimes accompanies the reaction of alcohols with DAST [95, 108], is seldom as extensive as with a-fluoroamines (FAR and 1,1,2,3,3,3 hexafluoropropyldiethylamine) but occurs in a few cases to the exclusion of fluonnation, thus, 9a-fluoro-11-hydroxysteroids give 9a fluoro-A -steroids [127, 128] Dehydration accompanied by Wagner-Meerwein rearrangement occurs during the fluonnation of testosterone [129] Intermolecular dehydration to form ethers in addition to fluorides is observed in the reaction of benzhydryl alcohols [104] (Table 6)... 

Testosterone enol diacetate reacts with perchloryl fluoride in aqueous dioxane to give 6a- and 6/i-fluorotestostcrone 17-acetatc (18 X = a-F, /i-F) as the major products along with 6a- and 6/3-hydroxytestosterone 17-acetate (18 X = a-OH, /j-OH) and also 17/i-hydroxyandrostane-3,6-dione 17-acctate.31 The enamine derivative 3-(pyrrolidin-l-yl)estra-3,5-dien-17/i-ol can be fluorinated in methanol at —25 to — 35 C to provide 4/J-fluoro-3a-methoxycstr-5-ene-3/f 17/ -diol (19),32 while various 2-fluoro-3-oxoestranc derivatives 20 are formed by fluorination of a number of 3-methoxyestrane derivatives in tetrahydrofuran/water mixture with perchloryl fluoride.33... 

Note. Testoral is also used as a proprietary name for testosterone. 9a-Fluoro- p, 17) -dihydroxy-17a-methylandrost-4-en-3-one C2oH29F03 = 336.4 CAS—76-43-7... 

Testosterone 3-dimethylhydrazone (S-115), l7a-methyltestosterone3-dimethylhydrazone (S-116), 3-methylene-17a-methylandrost-4-en-17 3-ol (S-26), 3-methylene-17a-ethylandrost-4-en-l7 0-ol (S-27), 9a-fluoro-3-methylene-17a-methylandrost-4-en-l 1/3,17 -diol (S-28), 5a-dihydro-... 

Testosterone. A 4-Chloro 17-acetate (S-114), 4-bromo (S-8), 4-methyl (S-11), 4-chloro 11/3-hydroxy 17-acetate (S-7), 4-fluoro 17-acetate (S-9), 4-hydroxy 17-acetate (S-10), la-methyl 4-chloro 17-acetate (S-79), 4-chloro 17-propionate (S-6), 4-hydroxy 17a-methyl (S-16), 4-chloro Ha-methyl (S-17), 4-mercapto 17a-methyl (S-49), 4-methylthio 17a-methyl (S-50), 4-ethylthio 17a-methyl (S-51), 4-acetylthio 17a-methyl (S-52), and 4-chloro 11/3-hydroxy 17a-methyl (S-102) substitutions all decrease the androgenic property. However, the anabolic potency is only slightly decreased and in a few cases increased, such as S-114, S-11, S-16, S-6. Substitution at the 4-position by bulky substituents i.e., 4-ethyl (S-13) and 4-allyl (S-14), abolishes both activities. 

Testosterone. 6p-Fluoro (S-62), 6)8 methyl (S-95), 6)8-nitro 17-acetate (S-39), 6)8-chloro 17-acetate (S-71), and 6)8-methyl 17a-methyl (S-97) substitutions all bring about a large decrease in the androgenic activity and in the anabolic activity. The ratio is not favorable. The 6/3-acetoxy 17-acetate (S-117) has a greatly reduced anabolic activity while the androgenic potency is not known. 

Testosterone. A 9a-Bromo 11/3-chloro (S-123), 9a-chloro 11/3-fluoro (S-125), 9o -bromo 11/3-fiuoro 17-propionate (S-124), A" 9o -chloro 11/3-chloro 17a-methyl (S-127), 9a-bromo 11/3-fluoro 17a-methyl (S-128), 9a-bromo 1 l/S-fluoro 17a-methyl (S-126), 3-methylene 9o -fluoro 11/3-hydroxy 17a-methyl (S-28), 9a-fluoro 1 IjS-hydroxy 16a-methyl Ha-methyl (S-132), and A " 16a-methyl 17a-methyl (S-131) substitutions all lead to decreased androgenic potencies and, with the exception of S-127, to decreased anabolic potencies. The anabolic-androgenic ratio is often favorable. The androgenic potency of the 9a-fluoro 11/3-hydroxy 17-... 

Ia-Methyl-A -11-ketotestosterone acetate (S-88), la-methyl-11-keto-testosterone acetate (S-84), 3,11,17-triketo-A -androstene (adrenos-terone) (S-43), and 1 l-keto-17a-methyltestosterone (S-24) all show decreased androgenic and anabolic potencies compared to the those 11-unsubstituted compound. However, introduction of a 9a-fluoro substituent into S-24 will increase both androgenic and anabolic activities to a... 

XXVI 12a-Chloro-ll/S-hydroxyprogesterone XXVII 21 -Fluoro-lla-acetoxyprogesterone XXVIII 6a-Methyl-17a-ethynyltestosterone XXIX 6a-Methyl -21 -ethyl -17a -ethynyl testosterone... 

Pyrrolidine in methanol added during a few min. to a refluxing soln. of testosterone in the same solvent under Ng- enamine (Y 98%) dissolved in methanol containing 10% water, treated with perchloryl fluoride at —20 during 20 min., kept at —20° until the exothermic reaction has ceased, then excess perchloryl fluoride removed by a vigorous stream of Ng —crude 3-oxo-4-fluoro-17/ -hydroxy-5-androstene (Y 83%) dissolved in dimethylformamide, coned. HCl added, and stored 20 hrs. at room temp. 4-fluorotestosterone (Y 80%). F. e. s. R. Joly and J. Warnant, Bl. 1961, 569. 

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