Title of Invention

A process for the preparation of (20R)-20,22-diethoxy-3B-tosyloxypregan-5-ene

Abstract

A process for the preparation of (20R)-20, 22-diethoxy- 3ß-tosyloxypregna-5-ene having structural formula 2 of the drawing accomanying this specification which comprises preparing the solution of (20R)-20, 22-diethoxy-3B-hydroxypregn a-5-ene in conventional organic basic solvent, adding Φ-toluene sulfonyl chloride to it keeping the reaction mixture in dark for a period in the range of 15-20 h, pouring the reaction mixture in aqueous solution of mild base, stirring the reaction mixture for a period in the range of 2-3 h, separating and purifying the product by conventional methods.

Full Text

This invention relates to a process for the preparation of (2OR)-20, 22-diethxy-3ß-tosyloxypregna-5-ene having structural formula 2. More particularly it relates a to preparation of the said compound using (2or)-20, 22-diethxy-3ß-hydroxypregna-5-ene having structural formula 1 in the drawing accompanying this specification. The product serves as a very useful intermediate for the synthesis of a new 20, 22-diethyoxy hexanor castasterone having structural formula 3 in the drawing accompanying the specification. Compound of formula 3 is a hexanor castasterone analogue. Chemically it is (2or)-2α, 3α-dihydroxy-20, 22-diethoxypregna-6-one. It is a plant growth promoting hormone and has shown promising plant growth promoting activity in mung bean epicotyl bioassay. It can be used for enhancing yields of several agricultural crops. Since, the compound 2 has not been reported in the literature so far, there is no known process available at present for its synthesis. The inventors in this patent application have reported a new process for the synthesis of compound 2 for the first time. Detailed procedure for the preparation of compound is given in our copending patent 3064/DEL/97. The main objective of this invention, therefore, is to provide a process for the preparation of (2or)-20, 22-diethxy-3ß-tosyloxypregna-5-ene having structural formula 2, using easily available reagents and simple reaction conditions. Accordingly, the present invention provides a process for the preparation of (2OR)-20, 22- diethoxy-3ß-tosyloxypregna-5-ene having structural formula 2 of the drawing accompanying this specification which comprises preparing the solution of (2OR)-20, 22-diethoxy-3ß-hydroxy pregna-5-ene in conventional organic basic solvent, adding p-toluene sulfonyl chloride to it keeping the reaction mixture in dark for a period in the range of 15-20 h, pouring the reaction mixture in ice cold aqueous solution of mild base, stirring the reaction mixture for a period in the range of 2-3 h, separating and purifying the product by conventional methods. In one of the embodiments of the present invention the basic organic solvent used may be such as pyridine,piperdine,triethylamine. In one of the embodiments of the present invention the mild base used may be such as KHCO3, NaHCO3. The solvent used for separation may be such as ethyl acetate, methylene dichloride, chloroform, diethyl ether. In a feature of the present invention the purification of the product may be carried out by coloumn chromatography on silica gel column using ethyl acetate-hexane as a solvent system. The process of the present invention is illustrated by the following examples, which should not be construed to limit the scope of this invention. Example 1 To a solution of compound 1 (0.70g, 2 mmol) in dry pyridine (5 ml), p-TsCl (0, 70g, 3.67 mmol) was added at 0°C. The reaction mixture was kept in dark for 12h at 30°C. It was then poured into 50 ml of ice cold 10%NaHCO3 solution and was kept for 2 h with occasional stirring. The solid formed was extracted with diethyl ether (3x50 ml). The ether layer was washed with water (2x50 ml), CuSO4 solution (3x50 ml),water (2x50 ml) and finally with brine (2x25 ml). The organic layer was dried over anhydrous sodium sulphate and ether was removed under reduced pressure to afford the tosylate 2 in quantitative yield (0.993g, 99%) as a pale yellow crystalline solid, m.p. 151-152°C; IR γmax 1720, 1458 cm-1; 1H-NMR (200 Mz) δ0.8 (s, 3H, 18-H3), 1.02 (s, 3H, 19-H3), 1.37 (s, 3H, 21-H3), 2.46 (s, 3H, tosyl CH3), 3.23 (bs, 1H, -OH), 4.21-4.48 (m, 1H, 3-H), 5.34 (d, 1H, J=5Hz, 6-H), 7.35 and 7.80 (AB pattern, 4H, J=8Hz, Ar), 9.58 (s, 1H, -CHO). Example 2 To a solution of compound 1 (0.35g, 1 mmol) in dry trietheylamine (2.5 ml), p-TsCl (0,35g, 1.84 mmol) was added at 0°C. The reaction mixture was kept in dark for 14h at 30°C. It was then poured into 50 ml of ice cold 10%NaHCO3 solution and was kept for 2 h with occasional stirring. The solid formed was extracted with diethyl ether (3x50 ml). The ether layer was washed with water (2x50 ml), CuSO4 solution (3x50 ml),water (2x50 ml) and finally with brine (2x25 ml). The organic layer was dried over anhydrous sodium sulphate and ether was removed under reduced pressure to afford the tosylate 2 in quantitative yield (0.43g, %) as a pale yellow crystalline solid, m.p. 151-152°C; IRγmax 1720, 1458 cm-1; 1H-NMR (200 Mz) δ0.8 (s, 3H, 18-H3), 1.02 (s, 3H, 19-H3), 1.37 (s, 3H, 21-H3), 2.46 (s, 3H, tosyl CH3), 3.23 (bs, 1H, -OH), 4.21-4.48 (m, 1H, 3-H), 5.34 (d, 1H, J=5Hz, 6-H), 7.35 and 7.80 (AB pattern, 4H, J=8Hz, Ar), 9.58 (s, 1H, -CHO). Example 3 To a solution of compound 1 (1.4g, 4 mmol) in dry pyridine (10 ml), p-TsCl (1.4g, 7.3 mmol) was added at 0°C. The reaction mixture was kept in dark for 16h at 30°C. It was then poured into 50 ml of ice cold 10%KHCO3 solution and was kept for 2 h with occasional stirring. The solid formed was extracted with diethyl etheM3xl00 ml). The ether layer was washed with water (2x50 ml), CuS04 solution (3x50 ml),water (2x50 ml) and finally with brine (2x25 ml). The organic layer was dried over anhydrous sodium sulphate and ether was removed under reduced pressure to afford the tosylate 2 in quantitative yield (2.27g, %) as a pale yellow crystalline solid, m.p. 151-152°C; IR ymax 1720, 1458 cm-1;1H-NMR (200 Mz) δ0.8 (s, 3H, 18-H3), 1.02 (s, 3H, 19-H3), 1.37 (s, 3H, 2I-H3), 2.46 (s, 3H, tosyl CH3), 3.23 (bs, 1H, -OH), 4.21-4.48 (m, 1H, 3-H), 5.34 (d, 1H, J=5Hz, 6-H), 7.35 and 7.80 (AB pattern, 4H, J=8Hz, Ar), 9.58 (s, 1H, -CHO). We Claim: 1. A process for the preparation of (2OR)-20, 22- diethoxy-3ß-tosyloxypregna-5-ene having structural formula 2 of the drawing accompanying this specification which comprises preparing the solution of (2OR)-20, 22-diethoxy-3ß-hydroxy pregna-5-ene in conventional organic basic solvent, adding p-toluene sulfonyl chloride to it keeping the reaction mixture in dark for a period in the range of 15-20 h, pouring the reaction mixture in ice cold aqueous solution of mild base, stirring the reaction mixture for a period in the range of 2-3 h, separating and purifying the product by conventional methods. 2. A process as claimed in claim 1 wherein the solvent used for the reaction is such as pyridine, piper dine, triethylamine. 3. A process as claimed in claims 1 and 2 wherein the mild base used is such as NaHCO3 and KHCO3. 4. A process as claimed in claims 1 to 3 wherein the solvent used for the separation is such as ethyl acetate, methylene dichloride, diethyl ether. 5. A process for the preparation of (2OR)-20, 22-diethoxy-3ß,-tosyloxypregna-5-ene as substantially described hereinbefore with reference to the drawing accompanying this specification and examples.

Documents:

3063-del-1997-abstract.pdf

3063-del-1997-claims.pdf

3063-del-1997-complete specification (granted).pdf

3063-del-1997-correspondence-others.pdf

3063-del-1997-correspondence-po.pdf

3063-del-1997-description (complete).pdf

3063-del-1997-drawings.pdf

3063-del-1997-form-1.pdf

3063-del-1997-form-2.pdf