反应详情

温度

5 °C

To a 3 L 3-neck RB flask with a mechanical stirrer, addition funnel, temperature probe and N2 inlet is added {4-[(3-chloro-4,7-difluorobenzothiophene-2-carbonyl)-(2-methoxy-5-pyridin-4-ylbenzyl)amino]cyclohexyl}methylcarbamic acid tert-butyl ester P6 (54.92 g, 83.70 mmol) and EtOH (1.5 L). The resulting beige slurry is cooled to 5° C. and concentrated HCl (800 mL) is added over 1 h. The cold bath is removed and the solution is stirred for 4.5 h at room temperature. The reaction mixture is concentrated by removing 1.5 L solvent in vacuo and H2O (500 mL) is added. The mixture is extracted with CH2Cl2 (2×350 mL). The aqueous layer is cooled to 2° C. and 50% NaOH (300 mL) is added to pH=13. The mixture is extracted with CH2Cl2 (3×600 mL) and the combined organic layers are washed with brine, dried over anhydrous Na2SO4, and concentrated in vacuo to give 3-chloro-4,7-difluoro-benzo[b]thiophene-2-carboxylic acid (2-methoxy-5-pyridin-4-ylbenzyl)-(4-methyl-aminocyclohexyl)amide n (46.5 g, 99%) as a tan foam.

1. additionTo a 3 L 3-neck RB flask with a mechanical stirrer, addition funnel
2. customThe cold bath is removed
3. concentrationThe reaction mixture is concentrated
4. customby removing 1.5 L solvent in vacuo and H2O (500 mL)
5. additionis added
6. extractionThe mixture is extracted with CH2Cl2 (2×350 mL)
7. temperatureThe aqueous layer is cooled to 2° C.
8. addition50% NaOH (300 mL) is added to pH=13
9. extractionThe mixture is extracted with CH2Cl2 (3×600 mL)
10. washthe combined organic layers are washed with brine
11. dry with materialdried over anhydrous Na2SO4
12. concentrationconcentrated in vacuo