反应详情

温度

45 °C

To a stirred solution of tert-butyl 2′-((hydroxyimino)methyl)-7′H-spiro[azetidine-3,5′-furo[3,4-b]pyridine]-1-carboxylate (0.520 g, 1.705 mmol, 1 eq) in DMF (12 mL) was added NCS (0.272 g, 2.046 mmol, 1.2 eq) at room temperature in dark under nitrogen atmosphere. Resulting reaction mixture was stirred at 45° C. for 1 hour. After chloro intermediate formation, 1,3-dichloro-2-fluoro-5-(1-trifluoromethyl-vinyl)-benzene (0.530 g, 2.046 mmol, 1.2 eq) was added followed by addition of KHCO3 (0.255 g, 2.557 mmol, 1.5 eq). Resulting reaction mixture was stirred at room temperature for 16 hours in dark under nitrogen atmosphere. After complete consumption of chloro intermediate, reaction mixture was quenched with water (100 mL) and extracted with ethyl acetate (3×100 mL). Combined organic layer was dried over anhydrous Na2SO4 and concentrated under reduced pressure to get brown thick oil (1.2 g, Crude). Crude compound was purified by column chromatography in 100-200 mesh size silica gel. Desired compound was eluted in 10% ethylacetate in hexanes to afford title compound as white semisolid (0.800 g, impure). Impure compound was used as such for next reaction. 1H NMR (400 MHz, CDCl3) δ: 1.46 (s, 9H), 3.84 (d, J=18.2 Hz, 1H), 4.10 (dd, J1=2.54 Hz, J2=9.5 Hz, 2H), 4.22 (d, J=18.16 Hz, 1H), 4.33 (dd, J1=3 Hz, J2=9.44 Hz, 2H), 5.02-5.10 (m, 2H), 7.56 (d, J=6 Hz, 2H), 7.84 (d, J=8.04 Hz, 1H), 8.03 (d, J=8.04 Hz, 1H). LC-MS (m/z): 59.6 (M−H).

1. customResulting
2. customreaction mixture
3. customResulting
4. customreaction mixture
5. stirringwas stirred at room temperature for 16 hours in dark under nitrogen atmosphere
6. customAfter complete consumption of chloro intermediate, reaction mixture
7. customwas quenched with water (100 mL)
8. extractionextracted with ethyl acetate (3×100 mL)
9. dry with materialCombined organic layer was dried over anhydrous Na2SO4
10. concentrationconcentrated under reduced pressure
11. customto get brown thick oil (1.2 g, Crude)
12. customCrude compound was purified by column chromatography in 100-200 mesh size silica gel
13. washDesired compound was eluted in 10% ethylacetate in hexanes