Triethylamine → HCID 67389745, compound

To a solution (188 mL) of benzyl ((1S)-2-{[tert-butyl(dimethyl)silyl]oxy}-4-hydroxy-1-isopropylbutyl)carbamate (14.9 g) in dehydrated THF was added triethylamine (5.07 g) and a solution (10 mL) of methanesulfonyl chloride (4.96 g) in dehydrated THF was added dropwise to the mixture under ice-cooling. After stirring at the same temperature for 1 hr, the reaction mixture was poured into a mixture of ethyl acetate and ice water and then the mixture was partitioned. The organic layer was washed with saturated brine, dried over anhydrous magnesium sulfate, and concentrated. To a solution (188 mL) of the residue in dehydrated THF was added with stirring under ice-cooling 1 mol/L potassium tert-butoxide—THF solution (37.7 mL), and the mixture was stirred at the same temperature for 1 hr. The reaction mixture was poured into a mixture of ethyl acetate and ice water and the mixture was partitioned. The organic layer was washed with saturated brine, dried over anhydrous magnesium sulfate, and concentrated. To a solution (188 mL) of the residue in dehydrated THF was added with stirring under ice-cooling 1 mol/L tetrabutylammonium fluoride—THF solution (37.7 mL), and the mixture was stirred at the same temperature for 1 hr and at room temperature for 5 hr. The reaction mixture was poured into a mixture of ethyl acetate and ice water and then the mixture was partitioned. The organic layer was washed with saturated brine, dried over anhydrous magnesium sulfate, and concentrated. The residue was purified by silica gel column chromatography (eluent: hexane-ethyl acetate/19/1→2/3) to give benzyl (2S)-3-hydroxy-2-isopropylpyrrolidine-1-carboxylate as colorless oil (yield: 3.22 g).

1. temperaturecooling
2. customthe mixture was partitioned
3. washThe organic layer was washed with saturated brine
4. dry with materialdried over anhydrous magnesium sulfate
5. concentrationconcentrated
6. additionTo a solution (188 mL) of the residue in dehydrated THF was added
7. stirringwith stirring under ice-
8. temperaturecooling 1 mol/L potassium tert-butoxide—THF solution (37.7 mL)
9. stirringthe mixture was stirred at the same temperature for 1 hr
10. additionThe reaction mixture was poured into a mixture of ethyl acetate and ice water
11. customthe mixture was partitioned
12. washThe organic layer was washed with saturated brine
13. dry with materialdried over anhydrous magnesium sulfate
14. concentrationconcentrated
15. additionTo a solution (188 mL) of the residue in dehydrated THF was added
16. stirringwith stirring under ice-
17. temperaturecooling 1 mol/L tetrabutylammonium fluoride—THF solution (37.7 mL)
18. stirringthe mixture was stirred at the same temperature for 1 hr and at room temperature for 5 hr
19. additionThe reaction mixture was poured into a mixture of ethyl acetate and ice water
20. customthe mixture was partitioned
21. washThe organic layer was washed with saturated brine
22. dry with materialdried over anhydrous magnesium sulfate
23. concentrationconcentrated
24. customThe residue was purified by silica gel column chromatography (eluent: hexane-ethyl acetate/19/1→2/3)

ORD record

ord-ad3f959402f041d2868191abbfd59c01

Source dataset

uspto-grants-2011_09

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US08013008B2