Organic compounds -- part of the class 532-570 series – Organic compounds – Heterocyclic carbon compounds containing a hetero ring...
Patent
1989-04-07
1990-12-11
Shah, Mukund J.
Organic compounds -- part of the class 532-570 series
Organic compounds
Heterocyclic carbon compounds containing a hetero ring...
552505, 552521, 552564, C07J 5100, C07J 4100
Patent
active
049772554
DESCRIPTION:
BRIEF SUMMARY
BACKGROUND OF THE INVENTION
1. Field of the Invention
This invention includes 17.alpha.-halo silyl ether steroidal 17.beta.-cyanohydrins useful as intermediates in the production of progesterones, 17-hydroxyprogesterones and corticoid pharmaceuticals as well as processes to produce and use the intermediates.
2. Description of the Related Art
Steroidal 17.beta.-cyano-17.alpha.-hydroxy-17-ethers are known, see for example, U.S. Pat. Nos. 4,500,461, 4,548,748 and 4,585,590 which disclose a variety of ethers including the silyl ethers, t-butyldimethyl silyl and TMS (trimethylsilyl). However, those ethers are not operable in the present invention, .alpha.-halo (halo) silyl ethers are known and have been used as precursors to silicon-stabilized nucleophilic carbanions. See particularly, Silicon in Organic Synthesis, E. Colvin, Butterworth, 1981, pp. 21-29, Synthesis 717 (1985), Tetrahedron Letters 25, 4245 (1984) and Journal of Organic Chemistry 48, 2110 (1983).
Mnay examples of intermolecular addition of carbon nucleophiles, such as methyl Grignard, to protected or unprotected cyanohydrins are known. For the unprotected cyanohydrin see Organic reactions, S. M. McElvain, vol IV, p. 264. For examples of addition of TMS protected cyanohydrins see Synthesis 270 (1981), Tetrahedron Letters 24, 4075 (1983) and Tetrahedron Letters 27, 1933 (1986).
This intermolecular reaction has been used to convert protected steroidal 17.beta.-cyanohydrins to pregnanes and corticoid derivatives, see U.S. Pat. Nos. 4,500,461, 4,548,748 and 4,585,590. Similar chemistry is also described in Bull. Chem. Soc. Japan 58, 978 (1985), Japan Kokai No. 57-062296, 57-062298, 57-062299 and 57-0622300 (Derwent Abstracts 82-42275E/21, 82-42277E/21, 82-42278E/21 and 82-42279E/21 respectively), Tetrahedron Letters 2005 (1971) and U.S. Pat. No. 3,697,510.
Deprontonation of .alpha.-halo silanes to afford nucleophiles is also known, see J. Am. Chem. Spc. 99, 4536 (1977), J. Chem. Soc. Chem. Comm. 513 (1977) and 297 (1978) and Tetrahedron 39, 867 (1983).
Silicon-stabilized carbanions are well known in the art, see E. Colvin, Silicon in Organic Synthesis, Butterworths, 1981. p. 21-29 and Synthesis 717 (1985). With regard to the formation of silicon-stabilized carbanion silyl ethers see J. Org. Chem., 48, 2110 (1983) and Tetrahedron Letters 25, 4245 (1984) where chloromethyl silyl ethers are reduced with magnesium to form the carbanion, which is added to a variety of electrophiles, but not nitriles. .alpha.-Lithio silyl carbanions are similarly prepared by reduction with lithium, J. Am. Chem. Soc., 76, 1619 (1954), and the corresponding sodium and potassium derivatives are known, J. Org. Chem. 26, 2604, (1961). With regard to the deportonation of the halomethyl silanes see J. Am. Chem. Soc., 99, 4536 (1977), J. Chem. Soc. Chem. Comm., 513 (1977), J. Chem. Soc. Chem. Comm., 297 (1978) and Tetrahedron 39, 867 (1983) where trimethylchloromethylsilane is deprotonated with sec-butyllithium. Although these latter silicon-stabilized carbanions have been added to a variety of electrophiles they have not been added to a nitrile carbon and have not been used in steroid chemistry.
Intramolecular cyclization incorporating a silyl ether in the ring are know, but are limited to radical cyclization onto carbon-carbon double and triple bonds and not to nitriles, see J. Org. Chem., 49, 2298 (1984), J. Am. Chem. Soc. 107, 500 (1985), Tetrahedron Letters 27, 2255 (1986), M. Koreeda presentation given at the 190th ACS National Meeting in Chicago on Sept. 11, 1985. The difficulty of promoting intramolecular free-radical cyclizations onto a nitrile is described in J. Org. Chem., 50, 5409 (1985). A process for cyclizing .omega.-halogenated nitriles using magnesium or lithium metal is discussed in J. Organometallic Chem. 87, 25 (1975). While that process uses .omega.-halogenated nitriles it is far different than the process of the present invention. The present invention requires an ether linkage, a silicon atom in the cyclizing sidechain and a steroid parent nucleus. Most impo
REFERENCES:
patent: 3967510 (1972-10-01), Bucourt
patent: 4081537 (1978-03-01), Hofmeister et al.
patent: 4500461 (1985-02-01), VanRheenen
patent: 4548748 (1985-10-01), VanRheenen
patent: 4585590 (1986-04-01), VanRheenen
Lehmann, Angew. Chem. Internation Ed. 4 (1965), No. 9, pp. 783-784.
Dyson et al., Tetrahedron Letters, 17, pp. 1841-1844, 1966.
Campbell, Tetrahedron Letters 25(42), pp. 4813-4816, 1984.
Chenera et al., J. Org. Chem., 1985, 50, 5409-10.
Cary and Sundberg, Advanced Organic Chemistry, Part A (New York, Plenum Press 1984), p. 236.
Amouroux, R. and Axiotis, G. P., Synthesis 270-272 (1981).
Anderson, R., Synthesis 717-734 (1985).
Burford, C., et al., J. Am. Chem. Soc. 99:4536-4537 (1977).
Burford, C., et al., Tetrahedron 39(6): 867-876 (1983).
Chenera, B., et al., J. Org. Chem. 50:5409-5410 (1985).
Colvin, E. W., Silicon in Organic Synthesis, Butterworth and Co., Ltd., 21-29 (1981).
Cooke, F. and Magnus, Ph., J. Chem. Soc. Chem. Comm., 513 (1977).
Gasc, J. C. and Nedelec, L., Tetrahedron Letters 22:2005-2008 (1971).
Gill, M., et al., Tetrahedron Letters 27(17):1933-1934 (1986).
Krepski, L. R., et al., Tetrahedron Letters 24(38):4075-4078 (1983).
Larcheveque, M., and Debal et Th. Cuvigny, A., J. Organometallic Chemistry 87:25-31 (1975).
Magnol, E. and Malacria, M., Tetrahedron Letters 27(20):2255-2256 (1986).
Magnus, P. and Roy, G., J. Chem. Soc. Chem. Comm. 297-298 (1978).
McElvain, S. M., Organic Reactions, vol. 4, John Wiley and Sons, Inc., 264-265 (1948).
Nishiyama, H., et al., J. Org. Chem. 49:2298-2300 (1984).
Nitta, I., et al., Bull. Chem. Soc. Japan 58:978-980 (1985).
Sakurai, et al., Tetrahedron Letters 27(1):75-76 (1986).
Seyferth, D. and Freyer, W., J. Org. Chem. 26:2604-2605 (1961).
Sommer, L. H. et al., J. Am. Chem. Soc., 76:1619-1621 (1954).
Stork, G. and Kahn, M., J. Am. Chem. Soc. 107:500-501 (1985).
Tamao, K., et al., J. Org. Chem. 48:2122-2124 (1983).
Tamao, K. and Ishida, N., Tetrahedron Letters 25(38):4245-4248 (1984).
Tamao, K. and Ishida, N., J. Organometallic Chem. 269:C37-C39 (1984).
Tamao, Ko et al., Tetrahedron 39(6):983-990 (1983).
Denmark Scott
Livingston Douglas A.
Pearlman Bruce A.
Shah Mukund J.
Stein Bruce
The Upjohn Company
Ward E. C.
LandOfFree
Steroidal 17.alpha.-silyl ethers and process to corticoids and p does not yet have a rating. At this time, there are no reviews or comments for this patent.
If you have personal experience with Steroidal 17.alpha.-silyl ethers and process to corticoids and p, we encourage you to share that experience with our LandOfFree.com community. Your opinion is very important and Steroidal 17.alpha.-silyl ethers and process to corticoids and p will most certainly appreciate the feedback.
Profile ID: LFUS-PAI-O-391132