Methyl iodide → HCID 68451539, compound

(1R*,4R*,5R*)-4-Iodo-6-oxabicyclo[3.2.1]octan-7-one (2.8 g) was dissolved in a solvent mixture of tetrahydrofuran (27 mL) and water (3 mL), and concentrated HCl (0.1 mL) was added thereto, followed by heating under reflux for 1 hour. The solvent was distilled away under reduced pressure, to thereby give (1R*,3R*,4R*)-3-hydroxy-4-iodocyclohexanecarboxylic acid (3.23 g) as a colorless solid. 2) The product obtained from the above-described reaction (3.22 g) was dissolved in tetrahydrofuran (50 mL), and borane-dimethyl sulfide complex (as 2M tetrahydrofuran solution, 47 mL) was added to the solution under ice cooling, followed by stirring at room temperature for 12 hours. The solvent was distilled away under reduced pressure, and the residue was dissolved in isopropanol (10 mL). To the solution was added 1N aqueous sodium hydroxide (12 mL) at room temperature, and the mixture was stirred for 12 hours. After the mixture was concentrated to about one-fifth of its original volume, the resultant mixture was diluted with water and methylene chloride, followed by stirring for 10 minutes. The organic layer was separated, and was sequentially washed with saturated aqueous ammonium chloride and saturated brine, followed by drying over anhydrous magnesium sulfate. The solvent was distilled away under reduced pressure, and the residue was purified by silica gel column chromatography (ethyl acetate:hexane=1:2), to thereby give (1R*,3R*,6S*)-7-oxabicyclo[4.1.0]hept-3-ylmethanol (1.25 g) as a colorless oily matter. 3) The product obtained from the reaction in the above step 2) (4.63 g) was dissolved in tetrahydrofuran (50 mL), and to the solution was added potassium bis(trimethylsilyl)amide (as 0.5N toluene solution, 80 mL) at −78° C., followed by stirring at the same temperature for 10 minutes, and methyl iodide (2.93 mL) was added thereto. The resultant mixture was heated to 0° C., and was stirred for 1 hour. Saturated aqueous ammonium chloride was added to the thus-obtained mixture, and the mixture was diluted with diethyl ether. The organic layer was separated, and was washed with saturated brine, followed by drying over anhydrous magnesium sulfate. The solvent was distilled away under reduced pressure, and the residue was purified by silica gel column chromatography (ethyl acetate:hexane=1:4), to thereby give the title compound (3.7 g).

1. additionwas added
2. temperatureby heating
3. temperatureunder reflux for 1 hour
4. distillationThe solvent was distilled away under reduced pressure
5. custom2) The product obtained from the above-described reaction (3.22 g)
6. distillationThe solvent was distilled away under reduced pressure
7. dissolutionthe residue was dissolved in isopropanol (10 mL)
8. additionTo the solution was added 1N aqueous sodium hydroxide (12 mL) at room temperature
9. stirringthe mixture was stirred for 12 hours
10. concentrationAfter the mixture was concentrated to about one-fifth of its original volume
11. additionthe resultant mixture was diluted with water and methylene chloride
12. stirringby stirring for 10 minutes
13. customThe organic layer was separated
14. washwas sequentially washed with saturated aqueous ammonium chloride and saturated brine
15. dry with materialby drying over anhydrous magnesium sulfate
16. distillationThe solvent was distilled away under reduced pressure
17. customthe residue was purified by silica gel column chromatography (ethyl acetate:hexane=1:2)
18. custom3) The product obtained from the reaction in the above step 2) (4.63 g)
19. stirringby stirring at the same temperature for 10 minutes
20. stirringwas stirred for 1 hour
21. customThe organic layer was separated
22. washwas washed with saturated brine
23. dry with materialby drying over anhydrous magnesium sulfate
24. distillationThe solvent was distilled away under reduced pressure
25. customthe residue was purified by silica gel column chromatography (ethyl acetate:hexane=1:4)

ORD record

ord-ab769c3a7c3446989cbb334bd5c3aca7

Source dataset

uspto-grants-2009_08

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US07576135B2