反应详情

To a solution of chlorosulfonyl isocyanate (0.52 mL, 5.96 mmol) in DCM (5 mL) was added t-butanol (0.57 mL, 6.00 mmol), drop-wise over 1-2 min and the reaction mixture was stirred at ambient temperature for 2 h. A suspension of compound 1-C (0.928 g, 5.00 mmol) in DCM (10 mL) was treated with pyridine (1 mL), the resulting solution cooled on an ice bath and the aforementioned reaction mixture was added drop-wise over 4 min. The reaction mixture was allowed to slowly warm to ambient temperature and stirred for 18 h. The reaction mixture was concentrated in vacuo, the residue dissolved in DCM (100 mL), washed with 1N HCl (25 mL), saturated NaHCO3 (25 mL), brine (25 mL), the organic phase dried over MgSO4, filtered, and evaporated under vacuum. The crude solid was triturated with DCM (10 mL), filtered, washed with DCM (2 mL) and air-dried to afford 0.602 g of compound 304-A as an off-white powder. 1H-NMR (DMSO-d6): δ 1.39 (s, 9H), 6.98 (s, 1H), 7.37-7.24 (m, 2H), 7.72 (d, 1H), 7.84 (d, 1H), 11.11 (s, 1H), 11.40 (s, 1H); MS: m/z 351.1 (MNa+).

1. temperaturethe resulting solution cooled on an ice bath
2. additionthe aforementioned reaction mixture was added drop-wise over 4 min
3. temperatureto slowly warm to ambient temperature
4. stirringstirred for 18 h
5. concentrationThe reaction mixture was concentrated in vacuo
6. dissolutionthe residue dissolved in DCM (100 mL)
7. washwashed with 1N HCl (25 mL), saturated NaHCO3 (25 mL), brine (25 mL)
8. dry with materialthe organic phase dried over MgSO4
9. filtrationfiltered
10. customevaporated under vacuum
11. customThe crude solid was triturated with DCM (10 mL)
12. filtrationfiltered
13. washwashed with DCM (2 mL)
14. customair-dried