Title of Invention

A PROCESS FOR THE PREPARATION OF (20R)-20-HYDROXY-3B-TOSYLOXYPREGNA-5-EN-22-ALDEHYDE

Abstract

A Process for the preparation of (20R)-20-hydroxy-3p- tosylpregna-5-en-22 aldehyde having structural formula 2, of the drawing accompanying this specification which comprises of preparing a solution of (20R)-20, 3-dihydroxy-CHO pregna-5-en-22-aldehyde in an organic solvent such as here in described adding p-toluenesulfonyl chloride to the solution, keepino the reaction mixture in dark for 10 to 15 hr, oouring the reaction mixture in an aqueous solution of an inorganic mild base, stirring the mixture for a period ranging between 1 to 2 hr, separating the solid bv conventional methods, washlna the solid with water and drying the product under reduced pressure and at ambient temperature to get (20R)-20-hydroxy-3ß-toSylpregna-5-en-22-aldehyde in pure form.

Full Text

This invention relates to a process for the preparation of a new compound (20R)-20-hydroxy-3p-tosylpregna-5-en-22-a!dehyde. The cornpoi..;J is having structural formula 2 as shown in the drawing accompanying this specification. More particularly it relates to the preparation of the said compound using (20R)-20,3p-dihydroxypregna-5-en-22-aldehyde having structural formula 1. The product serves as a very useful intermediate for the synthesis of a new 20, 22-diethoxy, hexanor castasterone having structural formula 3 in the drawing accompanying the specification. Compound of formula 3 is a hexanor castasterone analogue. Chemically it is (20R)-2a, 3a-dihydroxy-20, 22-diethoxy pregnan-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 of formula 2 has not been so far reported in the literature, there is no known process at present for its synthesis. The inventors in this present invention are reporting a new process for the synthesis of compound of formula 2 for the first time. Detailed procedure for the preparation of compound 1 is given in our co-pending patent No.3509/DEL/97. The main objective of this invention, therefore is to provide a process for the preparation of (20R)-20-hydroxy-3p-tosylpregna-5-en-22-aldehyde having structural formula 2. using easily available reagents _and simple reaction conditions. Accordingly, the present invention provides a process for the preparation of (20R)-20-hydroxy-3p-tosylpregna-5-en-22-aldehyde having structural formula 2, of the drawing accompanying this specification which comprises of preparing a solution of (20R)-20,3a-dihydroxypregna-5-en-22-aldehyde in an organic basic solvent such as here in described, adding p-toluenesulfonyl chloride to the solution, keeping the reaction mixture in dark for a period ranging between 10 to 15 hr, pouring the reaction mixture in an aqueous solution of an inorganic mild base, stirring the mixture for a period of 1 to 2 hr, separating the solid by conventional methods, washing the solid with water and drying under reduced pressure and at ambient temperature to get (20R)-20-hydroxy-3p-tosylpregna-5-en-22-aldehyde in pure form. In one of the embodiments of the present invention the mild base used may be such as sodium bicarbonate, potassium bicarbonate. In another embodiment of the present invention, the strength of the mild base ranges between 8 to 10%. In yet another embodiment of the invention the basic organic solvent used may be such as pyridine, triethyl amine, piperidine. 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 pyridine (5 ml), p-TsCI (0.70g, 2 mmol) was added a't 0°C and the reaction mixture was kept in dark for 12 h 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 was filtered, washed thoroughly and finally dried under reduced pressure at an ambient temperature to afford compound 2 as a pale yellow crystalline solid (0.993g, 100%), m.p. 151-52°C; 1H NMR (200 Mhz) 5 0.8 (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=5 Hz, 6-H), 7.35 and 7.80 (AB pattern. 4H. J=8Hz. Ar-H4), 9.58 (s, 1H, CHO). Example 2 To a solution of compound 1 (0.35g, 1 mmol) in piperidine (2.5 ml), p-TsCI (Q-.35g, 1 mmol) was added at 0°C and the reaction mixture was kept in dark for 14 h at 30°C. It was then poured into 25 ml of ice cold 10% KHCO3 solution and was kept for 2 h with occasional stirring. The solid was filtered, washed thoroughly and finally dried under reduced pressure at an ambient temperature to afford compound 2 as * n^ yollow crystalline solid (0 437g, 88%), m.p. 151-52°C; 1H NMR (200 Mhz) 5 0.8 (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=5 Hz, 6-H), 7.35 and 7.80 (AB pattern, 4H, J=8Hz, Ar-H4), 9.58 (s, 1H, CHO). Example 3 To a solution of compound 1 (0.35g, 1 mmol) in triethyl amine (2.5 ml), p-TsCI (0.35g, 1 mmol) was added at 0°C and the reaction mixture was kept in dark for 14 h at 30°C. It was then poured into 25 ml of ice cold 8% NaHCO3 solution and was kept for 2 h with occasional stirring. The solid was filtered, washed thoroughly and finally dried under reduced pressure at an ambient temperature to afford compound 2 as a pale yellow crystalline solid (0.421g, 85%), m.p. 151-52°C; 1H NMR (200 Mhz) 6 0.8 (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=5 Hz, 6-H), 7.35 and 7.80 (AB pattern, 4H, J=8Hz, Ar-H4), 9.58 (s, 1H, CHO). We Claim : 1. A process for the preparation of (20R)-20-hydrnxy-3ß-tosy!pregna 5en22- aldehyde having structural formula 2, of the drawing accompanying this specification which comprises of preparing a solution of (20R)-20,3ot- dihydroxypregna-5-en-22-aldehyde in an organic basic solvent such as here in described, adding p-toluenesulfonyl chloride to the solution, keeping the reaction mixture in dark for a period ranging between 10 to 15 hr, pouring the reaction mixture in an aqueous solution of an inorganic mild base, stirring the mixture for a period of 1 to 2 hr, separating the solid by conventional methods, washing the solid with water and drying under reduced pressure and at ambient temperature to get (20R)-20-hydroxy-3p- tosylpregna-5-en-22-aldehyde in pure form. 2. A process as claimed in claim 1 wherein the mild base used for quenching is such as sodium bicarbonate, potassium bicarbonate. 3. A process as claimed in claims 1 and 2 wherein the strength of the mild base used is in the range of 8 to 10%. 4. A process as claimed in claims 1 to 3 for the preparation of (20R)-20, 30- dihydroxypregna-5-en-22-aldehyde as substantially described hereinbefore with reference to the drawing accompanying this specification and examples.

Documents:

3060-del-1997-abstract.pdf

3060-del-1997-claims.pdf

3060-del-1997-complete specification (granted).pdf

3060-del-1997-correspondence-others.pdf

3060-del-1997-correspondence-po.pdf

3060-del-1997-description (complete).pdf

3060-del-1997-drawings.pdf

3060-del-1997-form-1.pdf

3060-del-1997-form-2.pdf

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