17-Methylprogesterone

Preparation of 11-Keto-6 -Methy progesterone 3,20-Bis-(Ethylene Ketal) A mixture of 5 g of 11-keto-6(3-methylprogesterone (Spero et al, 7. Am. them. Soc., 78, 6213 (1956)], 503 ml of benzene, 26 ml of ethylene glycol, and 0.152 g of p-toluenesulfonic acid monohydrate was stirred and heated under reflux for 22 hours while water was removed by means of a water trap. The reaction mixture was then cooled to 30°C, 0.4 ml of pyridine was added, and stirring was continued for 10 minutes. 

The reaction mixture was then shaken with 110 ml.of water and the organic and aqueous layers separated. The organic layer was dried over sodium sulfate and evaporated under diminished pressure giving a residue. The thus obtained residue was recrystallized from methanol giving 2.68 g of 11-keto-6j3-methylprogesterone 3,20-bis-(ethylene ketal) having a MP of 168° to 175°C. 

Preparation of 11 -Hydroxy-6a-Methylprogesterone A mixture of 2.68 g of 11-keto-6(3-methylprogesterone 3,20-bis-(ethylene ketal), 161 ml of tetrahydrofuran (previously distilled from lithium aluminum hydride), 1.34 g of lithium aluminum hydride and 14.5 ml of absolute ether was stirred and refluxed under nitrogen for 1.5 hours, then 27 ml of water was added cautiously, to decompose excess hydride. The resulting mixture was filtered and the filter cake was washed with 135 ml of ether. The combined filtrate and wash was shaken with 135 ml of water and separated. The aqueous layer was washed with four 55-ml portions of ether, then the organic layer and the washes were combined, washed once with water, and evaporated to dryness under diminished pressure leaving a tan residue. 

The thus-obtained residue was dissolved in a mixture of 268 ml of methanol and 26.8 ml of 3N aqueous sulfuric acid and heated under reflux for 40 minutes, with a color change from yellow to green. The reaction mixture was then cooled, neutralized by addition of 127 ml of 5% sodium bicarbonate solution, and concentrated under reduced pressure until almost all the methanol was removed. The resulting solid was removed by filtration, washed with water, dried, and twice crystallized from ethyl acetate to give 1.1 g of 11/3-hydroxy-Ba-methylprogesterone having a MP of 155° to 158°C, according to U.S. Patent 2,864,837. 

Premarin w/ Methylprogesterone) Estrogen, Conjugated w/ Methyltestosterone (Premarin w/ Methyltestosterone) Estradiol/... 

Estrogen, Conjugated + Methylprogesterone (Premarin + Methylprogesterone) [Estrogen Androgen Hormones]... 

HYDROXYMETHYLPHTHALIMIDE see HMPlOO N-(HYDROXYMETHYL)PHTHALIMIDE see HMPlOO 17-HYDROXY-6-METHYLPREGNA-4,6-DIENE-3,20-DIONE ACETATE see VTFOOO 17-HYDROXY-6-a-METHYLPREGN-4-ENE-3,20-DIONE ACETATE see MCAOOO 17-a-HYDROXY-6-a-METHYLPREGN-4-ENE-3,20-DIONE ACETATE see MCAOOO 17-a-HYDROXY-6-a-METHYLPROGESTERONE ACETATE see MCAOOO... 

Synonym 17a-Acetoxy-6a -methylprogesterone Source Asghari-Khiavi, M. Yamini, Y. Farajzadeh, M. A. J. Supercrit. Fluids (2004), 30(2), 111-117. 

Synonym 17a-Acetoxy-6-dehydro-6-methylprogesterone Source Dean, J. R. Kane, M. Khundker, S. Dowle, C. Tranter, R. L. Jones, P. Analyst 995), 120(8), 2153-2157. 

A 6-methylprogesterone derivative lacking oxygen at C3 exhibits the same biological activity as the parent drug the same holds true in the 19-nor series, as noted previously (see Chapter 4, Scheme 4.22). 

As in the 19-nor series, reaction of 17-hydroxy-6a-methylprogesterone (10-1) with ethylene dithioglycol proceeds to form the dithioacetal 16-1 (Scheme 6.16). Desulfurization by means of Raney nickel then yields the derivative with a methylene group instead of a ketone at C3 (16-2). Treatment of that intermediate with acetic anhydride in the presence of /1-toluenesulfonic acid gives the progestin angesterone (16-3). 

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