Water → Tert-butyl 5-(methoxymethylthio)-2-methylpentan-2-ylcarbamate

The tert-butyl 5-hydroxy-2-methylpentan-2-ylcarbamate (743 mg) obtained in Reference Example 239 was dissolved in pyridine (10 mL). To the solution, methanesulfonyl chloride (320 μL) was added, and the mixture was stirred at room temperature for 1 hour. To the reaction mixture, water (20 mL) was added, and the resultant mixture was then extracted with ethyl acetate (20 mL×4). The organic layer was dried over anhydrous sodium sulfate and then concentrated under reduced pressure. The residue was co-evaporated with toluene (10 mL×3), and the residue was then dissolved in DMF (13 mL). To the mixture, potassium carbonate (1.42 g) and thioacetic acid (490 μL) were added, and the mixture was stirred at room temperature for 2.5 hours. To the reaction mixture, water (25 mL) was added, and the resultant mixture was then extracted with ethyl acetate (25 mL). The organic layer was washed with water (20 mL) and brine (20 mL), dried over anhydrous sodium sulfate, and then concentrated under reduced pressure. The residue was dissolved in methanol (10 mL). To the mixture, sodium methoxide (369 mg) was added, and the mixture was stirred at room temperature for 30 minutes. The reaction mixture was concentrated under reduced pressure, an aqueous saturated ammonium chloride solution (15 mL) was then added thereto, and the resultant mixture was then extracted with ethyl acetate (20 mL×2). The organic layer was washed with brine (10 mL), dried over anhydrous sodium sulfate, and then concentrated under reduced pressure. The residue was dissolved in dichloromethane (5.0 mL). To the mixture, N,N-diisopropylethylamine (2.08 mL) and chloromethyl methyl ether (650 μL) were added, and the mixture was stirred at room temperature for 4 hours. To the reaction mixture, an aqueous saturated ammonium chloride solution (10 mL) was added, and the resultant mixture was then extracted with ethyl acetate (10 mL). The organic layer was washed with an aqueous saturated ammonium chloride solution (10 mL) and brine (10 mL), dried over anhydrous sodium sulfate, and then concentrated under reduced pressure. The residue was purified by silica gel column chromatography (15% ethyl acetate/hexane) to obtain the title compound (788 mg) as a colorless oil.

1. extractionthe resultant mixture was then extracted with ethyl acetate (20 mL×4)
2. dry with materialThe organic layer was dried over anhydrous sodium sulfate
3. concentrationconcentrated under reduced pressure
4. dissolutionthe residue was then dissolved in DMF (13 mL)
5. additionTo the mixture, potassium carbonate (1.42 g) and thioacetic acid (490 μL) were added
6. stirringthe mixture was stirred at room temperature for 2.5 hours
7. additionTo the reaction mixture, water (25 mL) was added
8. extractionthe resultant mixture was then extracted with ethyl acetate (25 mL)
9. washThe organic layer was washed with water (20 mL) and brine (20 mL)
10. dry with materialdried over anhydrous sodium sulfate
11. concentrationconcentrated under reduced pressure
12. dissolutionThe residue was dissolved in methanol (10 mL)
13. additionTo the mixture, sodium methoxide (369 mg) was added
14. stirringthe mixture was stirred at room temperature for 30 minutes
15. concentrationThe reaction mixture was concentrated under reduced pressure
16. additionan aqueous saturated ammonium chloride solution (15 mL) was then added
17. extractionthe resultant mixture was then extracted with ethyl acetate (20 mL×2)
18. washThe organic layer was washed with brine (10 mL)
19. dry with materialdried over anhydrous sodium sulfate
20. concentrationconcentrated under reduced pressure
21. dissolutionThe residue was dissolved in dichloromethane (5.0 mL)
22. additionTo the mixture, N,N-diisopropylethylamine (2.08 mL) and chloromethyl methyl ether (650 μL) were added
23. stirringthe mixture was stirred at room temperature for 4 hours
24. additionTo the reaction mixture, an aqueous saturated ammonium chloride solution (10 mL) was added
25. extractionthe resultant mixture was then extracted with ethyl acetate (10 mL)
26. washThe organic layer was washed with an aqueous saturated ammonium chloride solution (10 mL) and brine (10 mL)
27. dry with materialdried over anhydrous sodium sulfate
28. concentrationconcentrated under reduced pressure
29. customThe residue was purified by silica gel column chromatography (15% ethyl acetate/hexane)

ORD record

ord-386f47d1b0d740649acbf3bc29cb3e61

Source dataset

uspto-grants-2013_09

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US08530490B2