反应详情

温度

87.5 °C

A mixture of 4-(2-amino-2-methylpropyl)phenol acetic acid salt (45.06 g, 200 mmol), powdered K2CO3 (69.1 g, 500 mmol), and DMAC (550 mL) was heated to 75-100° C. Toluene (166 mL) was added, and the mixture was slowly heated to reflux at 134° C. The reflux temperature was raised by distillation of toluene and water into a water trap until the temperature reached 141° C. The mixture was then allowed to cool to below 100° C. at which point 4-fluorobenzonitrile (24.46 g, 202 mmol) was added along with 50 mL of toluene. The mixture was again heated to reflux at 140° C. with water being collected in a toluene-filled water trap for 4 h. The mixture was allowed to cool to room temperature, and the solids were filtered and rinsed with toluene. The filtrate was concentrated on a rotary evaporator to 77 g of syrup which was dissolved in EtOAc (400 mL). This solution was extracted with water (400 mL), and the aqueous layer was back-extracted with EtOAc (100 mL). The combined organic layers were washed with water (3×400 mL) and concentrated in vacuo to 53.4 g (100%) of oil which was >98% pure by HPLC analysis: 1H NMR (300 MHz, DMSO-d6) NMR was consistent with the desired product;

1. temperaturethe mixture was slowly heated
2. temperatureto reflux at 134° C
3. customreached 141° C
4. temperatureThe mixture was again heated
5. customcollected in a toluene-
6. additionfilled water trap for 4 h
7. temperatureto cool to room temperature
8. filtrationthe solids were filtered
9. washrinsed with toluene
10. concentrationThe filtrate was concentrated on a rotary evaporator to 77 g of syrup which
11. dissolutionwas dissolved in EtOAc (400 mL)
12. extractionThis solution was extracted with water (400 mL)
13. extractionthe aqueous layer was back-extracted with EtOAc (100 mL)
14. washThe combined organic layers were washed with water (3×400 mL)
15. concentrationconcentrated in vacuo to 53.4 g (100%) of oil which