反应详情

温度

0 °C

DIPEA (2.2 mL, 12.5 mmol) was added to 2-amino-5-methoxyphenol hydrochloride (1 g, 5.7 mmol) in THF (13 mL). The reaction mixture was cooled to 0° C., chloroacetyl chloride (0.5 mL, 6.3 mmol) was added portionwise and then stirred at 0° C. for 5 minutes. Further DIPEA (1.1 mL, 6.3 mmol) was added and the mixture was allowed to warm to r.t. and stirred for 3 days. The majority of the THF was removed in vacuo. EtOAc (50 mL) and water (50 mL) were added. The aqueous layer was extracted with EtOAc (2×50 mL) and the combined organic fractions were washed with brine (20 mL), dried (MgSO4), filtered and the solvent was evaporated in vacuo. To a portion of the crude material (0.250 g, 1.159 mmol) in MeCN (6 mL) was added potassium carbonate (0.449 g, 3.246 mmol) followed by THF (2 mL). The reaction mixture was stirred at r.t. for 5 h and then concentrated in vacuo. Water (5 mL) was added and the solid collected by filtration, washed with water (3×5 mL) and dried in vacuo to give the title compound (0.173 g, 17%) as a red solid. δH (DMSO-d6) 10.53 (1H, br s), 6.80 (1H, d, J 8.5 Hz), 6.58-6.51 (2H, m), 4.52 (2H, s), 3.69 (3H, s). LCMS (ES+) 180.1 (M+H)+, RT 2.27 minutes (Method 1).

1. temperatureto warm to r.t.
2. stirringstirred for 3 days
3. customThe majority of the THF was removed in vacuo
4. additionEtOAc (50 mL) and water (50 mL) were added
5. extractionThe aqueous layer was extracted with EtOAc (2×50 mL)
6. washthe combined organic fractions were washed with brine (20 mL)
7. dry with materialdried (MgSO4)
8. filtrationfiltered
9. customthe solvent was evaporated in vacuo
10. stirringThe reaction mixture was stirred at r.t. for 5 h
11. concentrationconcentrated in vacuo
12. additionWater (5 mL) was added
13. filtrationthe solid collected by filtration
14. washwashed with water (3×5 mL)
15. customdried in vacuo