反应详情

温度

21 °C

A mixture of 64.5 g of 2-fluoro-β(R)-(hydroxymethyl)benzenepropionitrile, 450 mL of toluene, and 106.2 g of triphenylmethyl chloride is stirred at 20-22° C. for 10 minutes to afford a brown solution; 54 g of triethylanine is added rapidly over a period of 10 minutes while maintaining an internal temperature of <30° C. The reaction mixture is stirred at an internal temperature of 35° C., (external temperature: 41° C.) for 24 hours to obtain a light, brown suspension. The tritylation reaction is catalyzed by water. The reaction progress is monitored by HPLC to determine if water addition is required. If after 4 hours, more than about 30% of starting material is left, 1 g of water is added. If after 20 hours, the amount of starting material is still more than 15%, an additional 1 g of water is added. After 24 hours, an additional 17 g of triphenylmethyl chloride and 7 g of triethylamine are added, the resulting suspension is stirred for an additional 24 hours at 35° C. and cooled to room temperature; 58 mL of methanol is added dropwise over 10 minutes, while maintaining an internal temperature of 30-35° C. The reaction mixture is stirred for 40 minutes at an internal temperature of 20-25° C. The mixture is concentrated under reduced pressure (20-50 mbar; bath temperature 45-50° C.) to obtain crude 2-fluoro-β(R)-[(triphenylmethyl)oxy]benzenepropionitrile as a red semi-solid. The semi-solid is suspended in 800 mL of methanol. The slurry is stirred at an internal temperature of 50° C. for 40 minutes, then at 20-22° C. for 30 minutes, and filtered to obtain, after washing the product with methanol and drying it under vacuum (30 mbar) at 45-50° C. for 4 hours or to constant weight, 2-fluoro-β(R)-[(triphenylmethyl)oxy]benzenepropionitrile; chiral purity:>99% ee.

1. customto afford a brown solution
2. addition54 g of triethylanine is added rapidly over a period of 10 minutes
3. temperaturewhile maintaining an internal temperature of <30° C
4. stirringThe reaction mixture is stirred at an internal temperature of 35° C., (external temperature: 41° C.) for 24 hours
5. customto obtain a light, brown suspension
6. customThe tritylation reaction
7. waitIf after 4 hours
8. waitIf after 20 hours
9. waitAfter 24 hours
10. stirringthe resulting suspension is stirred for an additional 24 hours at 35° C.
11. temperaturecooled to room temperature
12. temperaturewhile maintaining an internal temperature of 30-35° C
13. stirringThe reaction mixture is stirred for 40 minutes at an internal temperature of 20-25° C
14. concentrationThe mixture is concentrated under reduced pressure (20-50 mbar; bath temperature 45-50° C.)