反应详情

温度

22 °C

To a 2 L round bottom flask is added N-((4aS,7aS)-7a-(5-bromo-2-fluorophenyl)-4a,5,7,7a-tetrahydro-4H-furo[3,4-d][1,3]thiazin-2-yl)benzamide (35.0 g, 80.4 mmol), trifluoroacetamide (16.2 g, 143 mmol), copper(I) iodide (2.66 g, 13.7 mmol), sodium iodide (21.3 g, 141 mmol) and potassium carbonate (21.5 g, 153 mmol). The flask is capped with a septum, vacuum and back filled with nitrogen. 1,4-dioxane (731 mL) (previously degassed with vacuum-nitrogen) is added via cannula, and N,N′-dimethyl-, trans (+/−) 1,2-cyclohexanediamine (10.1 g, 70.8 mmol) is added. The mixture is placed in a preheated oil bath at 100° C. and stirred at this temperature for 19 h. The septum is replaced by a reflux condenser and a mixture of methanol (154 mL) and water (154 mL) is added through the condenser. The mixture is stirred at 100° C. for 3.5 h, cooled to 22° C., and concentrated partially under reduced pressure (to 0.6 L volume). Aqueous ammonium hydroxide (25%, 154 mL) is added and the mixture is stirred for 10 min. The mixture is extracted three times with ethyl acetate (3×500 mL) and the solvent is removed under reduced pressure. A residue is obtained that is purified by flash chromatography with a linear gradient of 50% to 75% ethyl acetate in hexane to give the title compound (14.9 g, 47%). ES/MS m/e: 372 (M+1).

1. customThe flask is capped with a septum, vacuum
2. additionback filled with nitrogen
3. custom1,4-dioxane (731 mL) (previously degassed with vacuum-nitrogen)
4. additionis added
5. customThe mixture is placed in a preheated oil bath at 100° C.
6. customThe septum is replaced by a reflux condenser
7. additionis added through the condenser
8. stirringThe mixture is stirred at 100° C. for 3.5 h
9. concentrationconcentrated partially under reduced pressure (to 0.6 L volume)
10. additionAqueous ammonium hydroxide (25%, 154 mL) is added
11. stirringthe mixture is stirred for 10 min
12. extractionThe mixture is extracted three times with ethyl acetate (3×500 mL)
13. customthe solvent is removed under reduced pressure
14. customA residue is obtained
15. customthat is purified by flash chromatography with a linear gradient of 50% to 75% ethyl acetate in hexane