反应详情

A suspension of 1-(6-(1-methyl-1H-pyrazol-4-yl)benzo[d]thiazol-2-yl)azetidin-3-ol (Reference Example 2, 0.143 g, 0.50 mmol) and Dess-Martin periodinane (1,1,1-tris(acetyloxy)-1,1-dihydro-1,2-benziodoxol-3-(1H)-one, CAS #87413-09-0, 0.636 g, 1.50 mmol) was stirred in 15:1 acetone/dimethyl sulfoxide (15 mL/1 mL). The reaction mixture was heated to near reflux for 4 hours, then additional Dess-Martin periodinane (0.212 g, 0.50 mmol) was added. The reaction was cooled to room temperature after an additional 3 hours of heating at near reflux. The reaction mixture was diluted with diethyl ether (15 mL) and insoluble material was removed by filtration. The filtrate was concentrated under reduced pressure to remove all but the dimethyl sulfoxide. This residue was partitioned between 9:1 CH2Cl2/hexane (20 mL) and water (10 mL). The organic layer was dried (Na2SO4) and filtered. The filtrate was concentrated under reduced pressure and the residue was purified by silica gel chromatography (90:10 to 40:60 CH2Cl2/ethyl acetate). Fractions containing product were combined and concentrated under reduced pressure to give a gummy solid, which after trituration with diethyl ether, provided 1-(6-(1-methyl-1H-pyrazol-4-yl)benzo[d]thiazol-2-yl)azetidin-3-one as a solid. 1H NMR (300 MHz, CDCl3) δ ppm 3.95 (s, 3H), 5.00 (s, 4H), 7.46 (dd, J=2, 8 Hz, 1H), 7.59 (s, 1H), 7.64 (d, J=8 Hz, 1H), 7.74 (d, J=2 Hz, 1H), 7.75 (s, 1H); MS (DCI/NH3) m/z 285 (M+H)+.

1. temperatureThe reaction mixture was heated
2. temperatureto near reflux for 4 hours
3. temperatureof heating at near reflux
4. customwas removed by filtration
5. concentrationThe filtrate was concentrated under reduced pressure
6. customto remove all but the dimethyl sulfoxide
7. customThis residue was partitioned between 9:1 CH2Cl2/hexane (20 mL) and water (10 mL)
8. dry with materialThe organic layer was dried (Na2SO4)
9. filtrationfiltered
10. concentrationThe filtrate was concentrated under reduced pressure
11. customthe residue was purified by silica gel chromatography (90:10 to 40:60 CH2Cl2/ethyl acetate)
12. additionFractions containing product
13. concentrationconcentrated under reduced pressure
14. customto give a gummy solid, which after trituration with diethyl ether