反应详情

To a stirred solution of (5-bromo-2-iodo-pyridin-3-yl)-methanol (9.5 g, 30.2 mmol, 1 eq) in dry THF (100 mL) was added i-PrMgCl.LiCl complex (1.3M in THF, 55.9 mL, 72.6 mmol, 2.4 eq) at −20° C. in drop wise manner over period of 20 minutes. Predissolved solution of N-boc-3-azetidinone (6.22 g, 36.3 mmol, 1.2 eq) in dry THF (80 mL) was added at −20° C. to above reaction mixture. Resulting reaction mixture was stirred at room temperature for 16 hours under nitrogen atmosphere. After maximum consumption of starting material, reaction mixture was cooled to 0° C. and quenched with 10% citric acid solution (20 mL), diluted with water (150 mL) and extracted with ethyl acetate (3×100 mL). Combined organic phase was washed with brine solution (100 mL), dried over anhydrous Na2SO4 and concentrated under reduced pressure to get yellowish sticky mass (18.2 g, crude). Crude compound was purified by column chromatography by using silica gel (100-200 mesh). Desired compound was eluted by 35% ethyl acetate in hexane to afford title compound as pale yellow thick oil (4.9 g, 45%). 1H NMR (400 MHz, CDCl3) δ: 1.43 (s, 9H), 3.12 (s, 1H), 4.13 (d, J=9.92 Hz, 2H), 4.54 (bs, 2H), 4.71-4.73 (m, 3H), 7.93 (d, J=2.12 Hz, 1H), 8.53 (d, J=3.00 Hz, 1H). LC-MS (m/z): 358.9 (M+H).

1. customResulting
2. customreaction mixture
3. customAfter maximum consumption of starting material, reaction mixture
4. temperaturewas cooled to 0° C.
5. customquenched with 10% citric acid solution (20 mL)
6. additiondiluted with water (150 mL)
7. extractionextracted with ethyl acetate (3×100 mL)
8. washCombined organic phase was washed with brine solution (100 mL)
9. dry with materialdried over anhydrous Na2SO4
10. concentrationconcentrated under reduced pressure
11. customto get yellowish sticky mass (18.2 g, crude)
12. customCrude compound was purified by column chromatography
13. washDesired compound was eluted by 35% ethyl acetate in hexane