SU449046A1 - The method of obtaining the triethylsilyl ethers of 17-oxysteroids - Google Patents

Description

This invention relates to a process for the preparation of the triethylamine esters of 17-oxysteroids possessing valuable therapeutical properties. A known method for producing dimethyl ethyl and megylate propylsilyl ethers of 17 oxy steroids is by reacting the 17 oxy steroid with the corresponding chlorosilane and hexaalkyldisilazane in pyridine. However, it is difficult to obtain unmixed ethers in a known manner: ethyl silyl ethers. In addition, at the end of the reaction, it is necessary to completely remove the pyridine from the reaction mixture in order to ensure the crystallization of the target esters. The proposed method for producing triethyl silyl agra 17D-hydroxysteroids of the general formula OJRj -PCH where is hydrogen, methyl; H Si (), is that the 17jB2 o J-oxysteroid is treated with hexaethyl disilazane and triethyl halo silane in dimethyl sulfoxide (DMSO) at room temperature. Triethyl bromosilane is commonly used as triethyl halo silane. Target products are isolated by known methods. Difficult to crystallize low melt triethylsilyloxy steroids from a mixture with high boilers (the reagents and their hydrolysis products are isolated by distillation of the latter under high vacuum followed by crystallization of the products. It is recommended to use chromatography on alumina for substances that undergo processing. the spectrum is taken in. hexane, and the IR spectrum is taken using CGH, aluminum oxide II, grade akg is used for chromatography Example 1. L7i-L-megyl-1, 4-Androstatdalen-17J5-ona-3 triethylsilyl ether. g (6.6 7 mmol) of ketol in IP ml of DM CO with 4.68 ml (16.5 mmop of hexaepyldisilazane and 1.15 ml (6.67 mmol of triegilbromosilane, a pale mixture of silazane and dimethylsulfoxide layer mixed with ammonium bromide and stirred for 4O min at room temperature, After 1 hour at 5 ° C, excess reagent is decomposed with 10 ml of isopropyl alcohol and stirred 15 minutes with 2OO ml of hexane and 25 ml of water while cooling with ice. The aqueous layer is separated, the hexane layer is washed with water and the combined aqueous extracts are further extracted with hexane . The hexane solution is filtered through a column of 20 g of alumina, washed with 60 ml of hexane and 4O ml of benzene. The residue after evaporation of the solvent was crystallized by disintegrating with pentane and 2.22 g (8O%) of the desired ester was isolated, t, nl, 117-12 ° C, m.p. an analytical sample of 127-128 ° C (pentane); . - -i20 + 21 ° (C 1, O5, dioxane); W D 234 nm (igL 4.16). -1 IR spectrum, cm 1660 (); 163O and 1610 (); () 1250 О о- /. / v 892, 745. 730 (shoulder); 710 Si () Found: C 75.71; H 10.56; 01 6.49. b 42 Calculated,%: C 75, DA; H 10.21; Si.6.77. PRI mme R 2. Triethylsilyl. Ether 17 L-methyltestosterone. A mixture of 1, OO g (3.30 mmol) of ketol with 2.32 ml (8.0 mmol) of hexaethyl disilazane and O, 57 ml (3.30 mmol) of triethyl bromosilane in 8 ml of DMSO is stirred for 2 hours at room temperature, treated similarly Example 1, and 2.60 g of the desired ester is obtained in the form of a partially crystallizing oil, from which 524 mg (41%) of product are isolated by trituration at -70 ° C, t, pl. 98-102 ° C. After evaporation in vacuum (up to 0 mm, 2 mm), 362 mg (26%) ether, g, melting point, was isolated from the mother liquor by low-temperature crystallization from pentane. 98-1О2 S.T. pl. analytical sample 1-10-10 ° C (pentane); TCJ. - + 57.6 (C 1, O4, dioxane); A 230.5 nm (t 4.24). 1680; 162O, 125O, IR spectrum, cm: 110O, 745, 730. Found,%: C 74.72; H 10.89; Si, 23. C, 74.96; H 1O, 65; Calculated, Si6,72, Triethylsilyl PRI me R 3. testosterone ether. 2, OO g (b, 94 mmol) of ketol, 8, O4 ml (27.70 mmol) of hexaethylamine and 2.48 ml (13.9 mmol) of triethylchlorosilane in 18 ml of DM CO are stirred for 3 hours at room temperature, incubated for 16 hours at 5 ° C and processed as in npAt.i3р 1. After filtering through 20 g of alumina, the hexane solution is evaporated first in a vacuum created by a water-jet pump and aaTet / r in a high vacuum (0.4-0.6 mm). From the residue (3.19 g of light yellow oil), after evaporation by trituration with pentane at -70 ° C, 1.75 g (63%) of e4} 1p, t, pl. 8 ° -82 ° C. T. pl, analytical sample 88-89 C (pentane); +82.5 (with 0.95, di (4.23). Ocean); D230 1620, 1240, IR spectrum, cm: 1680, 1O85, 885, 745, 73O. Found,%: C 74.15; H 10.53; Si 6.92. 5 2 2 Calculated,%: C, 74.57; H 1O, 51; Si6.95, Example 4: 19-nor testosterone triethylsilyl ether. A mixture of 2, OO g (7.32 mmol) of ketol with 6.36 ml (21.98 mmol) of hexaethyl disilazane and 1.96 ml (10.98 mmol) of triethyl bromosilane in 16 ml of DMSO is stirred for 45 minutes at room temperature, treated, j as in example 1, the residue (3.99 g of yellow oil) after evaporation in vacuum (up to 2 mm) is dissolved in 15 ml of hexane and applied to a column with 15O g of alumina. The column is washed with 25O-ML hexane and 300 ml of a mixture of 30% methylene chloride in benzene, eluting with 1.65 g of ether as an oil, with preparative

By thin-layer chromatography of which (0.7 g) on alumina (4OOx250x x2 mm), a strongly crystallizing ether is isolated. T, pl. analytical sample

79-81 ° C; + 44.3 (C 1, O8, lajjj

dioxane): D230 nm (tq 4.23).

Mks

IR spectrum, 1665, 1615, 1245, 1105, 1090, 890, 745, 728.

Found,%; C 74.23; H 10.49; $ 1 7.26.

 C, 74.17; H 1O, 37; 3i

Calculated 7.23.

Subject invention

Claims (2)

1. A process for the preparation of the triethylsilyl ethers of 175-hydroxysheroids of the general formula ten methyl; R where is hydrogen, Si (C "H) characterized in that the l / ia -oxyetheroid is treated with hexaethyl disilazane and triethyl halide in imethyl sulfoxide, followed by isolation of spruce products in a known manner. 2. A method according to claim 1, characterized in that griethyl bromosilane is used as a griethyl halide silane.