Sparteine → 3-[(2R,3S)-2-{[(4S)-4-benzyl-2-oxo-1,3-thiazolidin-3-yl]carbonyl}-5-(4'-fluorobiphenyl-4-yl)-3-hydroxypentyl]-1,2,3-benzotriazin-4(3H)-one

Temperature

0 °C

In a flame-dried flask, 3-{3-[(4S)-4-benzyl-2-oxo-1,3-thiazolidin-3-yl]-3-oxopropyl}-1,2,3-benzotriazin-4(3H)-one (0.25 g) was taken up in dichloromethane (10 mL) and cooled to 0° C. Titanium tetrachloride (0.76 mL, 1 M solution) was added drop-wise and the reaction mixture was stirred for 10 to 15 minutes. (−)-Sparteine (0.36 mL) was added slowly to the reaction mixture and stirred at 0° C. for 20 minutes. A solution of the compound obtained from step e above (0.17 g) in dichloromethane (10 mL) was added slowly, and stirring was continued at 0° C. After 3 hours, the reaction was quenched with the drop-wise addition of saturated ammonium chloride solution, and dichloromethane was added. The organic layer was separated and the aqueous layer was extracted with dichloromethane. The organic layer was washed with brine, dried over anhydrous sodium sulphate, and concentrated under reduced pressure. The crude product thus obtained was purified by silica gel flash column chromatography using 30% ethyl acetate in hexane as eluant to afford the title compound (0.2 g).

1. stirringstirred at 0° C. for 20 minutes
2. stirringstirring
3. customwas continued at 0° C
4. waitAfter 3 hours
5. customthe reaction was quenched with the drop-wise addition of saturated ammonium chloride solution, and dichloromethane
6. additionwas added
7. customThe organic layer was separated
8. extractionthe aqueous layer was extracted with dichloromethane
9. washThe organic layer was washed with brine
10. dry with materialdried over anhydrous sodium sulphate
11. concentrationconcentrated under reduced pressure
12. customThe crude product thus obtained
13. customwas purified by silica gel flash column chromatography

ORD record

ord-875e3d173bb9491faad5cf74d30f8873

Source dataset

uspto-grants-2014_09

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US08846910B2