Sodium Iodide → HCID 58154265, compound

A solution of zinc borohydride (0.25 M in diethyl ether, 3.48 mL, 0.87 mmol) was added dropwise over a 5 minute period to a stirred, cooled (ice-bath) suspension of 6′-bromo-4,4-bis(2-chloroethoxy)spiro[cyclohexane-1,3′-indolin]-2′-one (preparation 14a, 0.81 g, 1.9 mmol) in dichloromethane (5 mL). Subsequently, trimethylsilyl chloride (0.46 mL, 3.64 mmol) was added dropwise and the mixture was warmed to ambient temperature and stirred overnight. Saturated aqueous sodium hydrogen carbonate solution and ethyl acetate were added to the mixture and stirring was continued for 1 hour. The organic layer was separated, washed with brine, dried (MgSO4) and evaporated to give a white solid. The solid was taken up in N,N′-dimethylformamide (6 mL), morpholine (0.45 mL, 5.1 mmol) and sodium iodide (0.2 g, 1.6 mmol) were added, and the mixture was heated with stirring to 85° C. in a sealed tube. After stirring overnight, the mixture was diluted with water, saturated aqueous sodium hydrogen carbonate solution was added and the mixture was extracted with ethyl acetate. The organic layer was extracted with 2M aqueous hydrochloric acid solution (3×20 mL) and the combined aqueous layer was washed with ethyl acetate. The resulting aqueous solution was made strongly basic with solid sodium hydroxide and then extracted with ethyl acetate. The organic layer was dried (MgSO4) and evaporated and the residue was purified by flash chromatography (100:1 to 25:1 dichloromethane/methanol) to give the title compound (0.21 g, 28%, 92:8 mixture of isomers) as a white solid.

1. temperaturecooled
2. stirringstirring
3. waitwas continued for 1 hour
4. customThe organic layer was separated
5. washwashed with brine
6. dry with materialdried (MgSO4)
7. customevaporated
8. customto give a white solid
9. temperaturethe mixture was heated
10. stirringwith stirring to 85° C. in a sealed tube
11. stirringAfter stirring overnight
12. additionwas added
13. extractionthe mixture was extracted with ethyl acetate
14. extractionThe organic layer was extracted with 2M aqueous hydrochloric acid solution (3×20 mL)
15. washthe combined aqueous layer was washed with ethyl acetate
16. extractionextracted with ethyl acetate
17. dry with materialThe organic layer was dried (MgSO4)
18. customevaporated
19. customthe residue was purified by flash chromatography (100:1 to 25:1 dichloromethane/methanol)

ORD record

ord-ddacd0c39d7342848cd9b294cec8c1dd

Source dataset

uspto-grants-2013_05

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US08450341B2