Boron trifluoride etherate → Imidazolin-2-one, 8

Temperature

-78 °C

To a solution of compound 23G (150 mg, 0.5 mmol) in anhydrous THF (12 mL) cooled to −78° C. was added dropwise 1.0 M LiEt3BH solution in THF (0.5 mL, 0.5 mmol). After addition, the reaction was stirred at −78° C. for 4 h, then quenched by addition of saturated aqueous Na2CO3 (5 mL). The reaction was warmed to 0° C., 30% H2O2 (˜0.5 mL) was added, and the reaction was stirred at 0° C. for 30 min, then extracted with CH2Cl2 (3×). The combined extracts were washed with brine, dried (Na2SO4), filtered, and concentrated under reduced pressure overnight. The residue (˜120 mg) was dissolved in anhydrous CH2Cl2, and to the resulting solution cooled to −78° C. was added dropwise triethylsilane (0.5 mL, 3.1 mmol), followed by boron trifluoride diethyl etherate (0.5 mL, 3.9 mmol). The reaction mixture was stirred at −78° C. for 2 h, then additional triethylsilane (0.3 mL, 1.88 mmol) and boron trifluoride diethyl etherate (0.3 mL, 2.35 mmol) were added, and the reaction was stirred at 0° C. overnight. The reaction was then quenched with saturated aqueous Na2CO3 (10 mL), then extracted with CH2Cl2 (3×). The combined extracts were washed with brine, dried (Na2SO4), filtered, and concentrated under reduced pressure to give a crude product (˜100 mg). The crude product was purified using preparative HPLC to give 30 mg, which was further purified using chiral preparative HPLC to afford the title compound (9 mg). HPLC: 98% at 4.39 min (retention time) (Conditions: Zorbax SB C18 (4.6×75 mm); Eluted with 0% to 100% B, 8 min gradient (A=90% H2O-10% MeOH-0.1% H3PO4 and B=10% H2O-90% MeOH-0.1% H3PO4); Flow rate at 2.5 mL/min UV detection at 220 nm). Chiral HPLC: retention time=10.59 min (99%); Conditions: OD (4.6×250 mm); Eluted with 20% isopropanol in hexane for 30 min at 1 mL/min; MS (ES) m/z 292 [M+1]+.

1. additionAfter addition
2. customquenched by addition of saturated aqueous Na2CO3 (5 mL)
3. temperatureThe reaction was warmed to 0° C.
4. addition30% H2O2 (˜0.5 mL) was added
5. stirringthe reaction was stirred at 0° C. for 30 min
6. extractionextracted with CH2Cl2 (3×)
7. washThe combined extracts were washed with brine
8. dry with materialdried (Na2SO4)
9. filtrationfiltered
10. concentrationconcentrated under reduced pressure overnight
11. dissolutionThe residue (˜120 mg) was dissolved in anhydrous CH2Cl2
12. temperatureto the resulting solution cooled to −78° C.
13. stirringThe reaction mixture was stirred at −78° C. for 2 h
14. stirringthe reaction was stirred at 0° C. overnight
15. customThe reaction was then quenched with saturated aqueous Na2CO3 (10 mL)
16. extractionextracted with CH2Cl2 (3×)
17. washThe combined extracts were washed with brine
18. dry with materialdried (Na2SO4)
19. filtrationfiltered
20. concentrationconcentrated under reduced pressure
21. customto give a crude product (˜100 mg)
22. customThe crude product was purified
23. customto give 30 mg, which
24. customwas further purified

ORD record

ord-808928d336834626b02ca9b679341b02

Source dataset

uspto-grants-2010_08

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US07772267B2