Water → benzyl (2S,3S)-3-{[tert-butyl(dimethyl)silyl]oxy}-2-isopropylpyrrolidine-1-carboxylate

To a solution (10 mL) of ethyl (3S,4S)-4-{[(benzyloxy)carbonyl]amino}-3-hydroxy-5-methylhexanoate (700 mg) in tetrahydrofuran were added 2,6-lutidine (0.504 mL) and tert-butyldimethylsilane trifluoromethanesulfonate (0.596 mL), and the mixture was stirred at room temperature for 30 min. Water was added to the reaction mixture and the mixture was extracted with ethyl acetate. The extract was washed with 1 mol/L hydrochloric acid, saturated aqueous sodium hydrogencarbonate solution and saturated brine, dried over anhydrous sodium sulfate and concentrated under reduced pressure. To a solution of the residue in tetrahydrofuran (5 mL)-ethanol (1 mL) was added lithium borohydride (94 mg), and the mixture was stirred at room temperature for 1 hr. Water was added to the reaction mixture and the mixture was extracted with ethyl acetate. The extract was washed with saturated brine, dried over anhydrous sodium sulfate and concentrated under reduced pressure. To a solution (10 mL) of the residue in tetrahydrofuran were added triethylamine (0.602 mL) and methanesulfonyl chloride (0.25 mL), and the mixture was stirred at room temperature for 1 hr. Water was added to the reaction mixture and the mixture was extracted with ethyl acetate. The extract was washed with 1 mol/L hydrochloric acid, saturated aqueous sodium hydrogencarbonate solution and saturated brine, dried over anhydrous sodium sulfate and concentrated under reduced pressure. The residue was dissolved in tetrahydrofuran (10 mL), potassium tert-butoxide (363 mg) was added thereto under ice-cooling, and the mixture was stirred at room temperature for 18 hr. Water was added to the reaction mixture, and the mixture was extracted with ethyl acetate. The extract was washed with 0.1 mol/L hydrochloric acid, saturated aqueous sodium hydrogencarbonate solution and saturated brine, dried over anhydrous sodium sulfate and concentrated under reduced pressure. The residue was purified by silica gel column chromatography (developing solvent: hexane:ethyl acetate=9:1→5:1) to give the title compound (yield: 441 mg) as a pale-yellow oil.

1. extractionthe mixture was extracted with ethyl acetate
2. washThe extract was washed with 1 mol/L hydrochloric acid, saturated aqueous sodium hydrogencarbonate solution and saturated brine
3. dry with materialdried over anhydrous sodium sulfate
4. concentrationconcentrated under reduced pressure
5. additionTo a solution of the residue in tetrahydrofuran (5 mL)-ethanol (1 mL) was added lithium borohydride (94 mg)
6. stirringthe mixture was stirred at room temperature for 1 hr
7. additionWater was added to the reaction mixture
8. extractionthe mixture was extracted with ethyl acetate
9. washThe extract was washed with saturated brine
10. dry with materialdried over anhydrous sodium sulfate
11. concentrationconcentrated under reduced pressure
12. additionTo a solution (10 mL) of the residue in tetrahydrofuran were added triethylamine (0.602 mL) and methanesulfonyl chloride (0.25 mL)
13. stirringthe mixture was stirred at room temperature for 1 hr
14. additionWater was added to the reaction mixture
15. extractionthe mixture was extracted with ethyl acetate
16. washThe extract was washed with 1 mol/L hydrochloric acid, saturated aqueous sodium hydrogencarbonate solution and saturated brine
17. dry with materialdried over anhydrous sodium sulfate
18. concentrationconcentrated under reduced pressure
19. dissolutionThe residue was dissolved in tetrahydrofuran (10 mL)
20. additionpotassium tert-butoxide (363 mg) was added
21. temperatureunder ice-cooling
22. stirringthe mixture was stirred at room temperature for 18 hr
23. additionWater was added to the reaction mixture
24. extractionthe mixture was extracted with ethyl acetate
25. washThe extract was washed with 0.1 mol/L hydrochloric acid, saturated aqueous sodium hydrogencarbonate solution and saturated brine
26. dry with materialdried over anhydrous sodium sulfate
27. concentrationconcentrated under reduced pressure
28. customThe residue was purified by silica gel column chromatography (developing solvent: hexane:ethyl acetate=9:1→5:1)

ORD record

ord-31048ace10884c39b5e722e6b35d9f8b

Source dataset

uspto-grants-2013_11

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US08592452B2