4-Toluenesulfonyl chloride → HCID 86736793, compound

To a nitrogen blanketed, ice-cooled, stirred suspension of 1.08 g of 35% potassium hydride in mineral oil in 58 ml dry tetrahydrofuran and 2-3 ml triglyme add 3.49 g 3-(3-hydroxy-1-azetidinyl)-5α-cholestane (a mixture of the 3α- and 3β-epimers). Continue stirring the mixture for 5 days at room temperature, adding an additional 80 ml dry tetrahydrofuran after the first 24 hours. After 5 days add a solution of 1.52 g of p-toluenesulfonyl chloride in 10 ml tetrahydrofuran and stir one hour. Destroy the excess potassium hydride by the cautious addition of approximately 70 ml of water-saturated ethyl ether; then, add 350 ml water and saturate with sodium chloride. Extract once with 300 ml ethyl ether and then twice with 150 ml portions of ethyl ether. Combine the etheral extracts, dry over anhydrous sodium sulfate, and acidify the solution with a solution of 0.93 g maleic acid in 50 ml ethyl ether. Filter the crude maleate salt and triturate with 150 ml hexane. Dissolve the triturated material in 20 ml methylene chloride and treat the solution with decolourizing carbon. Filter the carbon and dilute the filtrate with 250 ml isopropyl ether. Concentrate the solution in vacuo until a precipitate begins to form. Filter the precipitate to obtain the maleate salt of the title compound, m.p. 105°-109° C. dec. (a mixtuer of 3α- and 3β- epimers).

1. temperatureice-cooled
2. additiona mixture of the 3α- and 3β-epimers)
3. stirringContinue stirring the mixture for 5 days at room temperature
4. stirringstir one hour
5. customDestroy the excess potassium hydride
6. additionby the cautious addition of approximately 70 ml of water-saturated ethyl ether
7. additionthen, add 350 ml water
8. concentrationsaturate with sodium chloride
9. extractionExtract once with 300 ml ethyl ether
10. dry with materialdry over anhydrous sodium sulfate
11. filtrationFilter the crude maleate salt
12. customtriturate with 150 ml hexane
13. dissolutionDissolve the triturated material in 20 ml methylene chloride
14. additiontreat the solution with decolourizing carbon
15. filtrationFilter the carbon
16. additiondilute the filtrate with 250 ml isopropyl ether
17. concentrationConcentrate the solution in vacuo until a precipitate
18. customto form
19. filtrationFilter the precipitate

ORD record

ord-676d7106b4fe41eda454147c1b701ea9

Source dataset

uspto-grants-1980_01

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US04183923