17a-hydroxyprogesteron

Androst-4-ene-3,17-dione 17a-Hydroxyprogesterone (1 g) is dissolved in 10 ml of pyridine and treated dropwise at —20° with a solution of nitrosyl chloride in pyridine until a permanent blue color develops. The reaction is quenched with 500 ml of ice water, and the resulting nitrite is filtered and... 

Preparation of 17a-Hydroxyprogesterone 3,20-Bis-(Ethylene Keta/J A solution was prepared containing 50.0 g of 17a-hydroxyprogesterone in 1,000 ml of ben2ene, 100 ml of ethylene glycol and 2.5 g of p-toluenesulfonic acid monohydrate. This mixture was re-... 

The lower glycol layer was separated and washed with benzene. The benzene layer and the benzene washings were combined and the combined solution was divided into two equal portions, one of which was used for the isolation of 17a-hydroxyprogesterone 3,20-bis-(ethylene ketal) as follows. The benzene solution was washed with 5% sodium carbonate solution, water and saturated sodium chloride solution. After being dried over anhydrous magnesium sulfate the solution was concentrated to dryness at reduced pressure. 

The solution was then refrigerated overnight and 17.8 g of crystals were removed by filtration. A second crop was obtained yielding 3.7 g of compound. The total yield of 17a-hydroxyprogesterone 3,20-bis-(ethylene ketal) was 20.3 g (64.3% of theory). Recrystallization of the crude 17a-hydroxyprogesterone 3,20-bis-(ethylene ketal) from methanol gave the pure bisketal of MP 209° to 211°C. 

Preparation of 5a,6a-0xido-17a-Hydroxya//opregnane-3,20-dione 3,20-Bis-(Ethy ene Ketal) A solution was prepared by heating 19.96 g (0.0477 mol) of 17a-hydroxyprogesterone 3,20-bis-(ethylene ketal) and 500 ml of benzene. After the solution was effected the flask was cooled to 5°C and a mixture of 3.68 g (0.0449 mol) of sodium acetate and 174 ml of 40% peracetic acid was added with stirring. The reaction mixture was stirred in the ice bath for 3 hours. The lower peracid layer was separated, diluted with water and extracted twice with benzene. 

FIGURE 9 Moderately rapid gradient separation. Column XTerra MS C, IS, 4.6x 20mm 3.5p.m. Gradient 0 to 100% B over 4min,A 0.1% formic acid in water, B 0.1% formic acid in acetonitrile. Flow rate 3.0mL/min. Temperature 30°C. Detection UV at 254 nm. Instrument Alliance 2795 with 996 photodiode array detector. Compounds (I) acetanilide, (2) triamcinolone, (3) hydrocortisone, (4) 2-amino-7-chloro-5-oxo-5H-[l]benzopyrano[2,3-b]pyridine-3-carbonitrile, (5) 6a-methyl-17a-hydroxyprogesterone, (6) 3-aminofluoranthene, (7) 2-bromofluorene, (8) perylene, (9) naphtho(2,3-a)pyrene. 

Chlorination of steroids (4, 264-265 5, 352-353 6, 298-299). Breslow s method for chlorination of steroids at CV has been developed into a useful method for conversion of 17a-hydroxyprogesterone (1) into the triene (4), a useful intermediate to highly active corticoids.2 The hindered I7a-hydroxyl group is esterified with m-iodobenzoic anhydride and 4-dimethylaminopyridine. Irradiation of the ester (2) with C6H5IC12 in the presence of NaOAc (HC1 scavenger) affords 3 in quantitative... 

The pL (L = H or D) dependence of the solvent DIEs associated with progesterone 493 oxidation to 17a-hydroxyprogesterone 494 and 17-0-acetyltestosterone 495 and 17a-hydroxyprogesterone oxidation to androstenedione 496 has been determined in microcosms from pig testes580 (equation 290). The initial rate of oxidation of 493 to 494 has been associated with the pL-independent inverse solvent isotope effect (SIE) (fce/ D = 0.75 — 0.95 in 30% DOD) while the oxidation of 495 has been associated with the pL-independent positive SIE in 30% DOD (ku/ku of about 2), DOD inhibited the formation of 496 from 444 in noncompetitive in pL-dependent manner. Androgens are synthesized from progesterone in a two-step reaction involving the 17a-hydroxylation... 

Preparation of 6a-Methyl-17-Hydroxyprogesterone 17-Acetate 1 g of 6a-methyl-17a-hydroxyprogesterone was dissolved in a mixture of 10 ml of acetic acid and 2 ml of acetic anhydride by heating. After solution was effected the mixture was cooled to 15°C, and 0.3 g of p-toluenesulfonic acid was added. After allowing the mixture to stand for a period of 2.5 hours at room temperature, the pink solution was poured into ice water to give an amorphous solid which was recovered by filtration. 

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