反应详情

温度

5 °C

A 3 liter three-neck mechanically stirred flask under N2 containing a solution of 3-fluoro-N-phenylaniline (86 g, 460 mmol) in 1.2 L dichloromethane was cooled in an ice bath to 0° C., and then triphosgene (150 g, 505 mmol) was added. A solution of pyridine (52 mL, 640 mmol) in dichloromethane (200 mL) was added in a dropwise fashion. Initial addition resulted in a temperature spike to 25° C. after the first 10 mL had been added over 10 min. The addition was paused, and the reaction mixture was stirred for 1 h while cooling to 5° C. Addition of the pyridine solution was again commenced at a rate of 5 mL/min, at which a reaction temperature of 5-10° C. was maintained. After addition was complete (about 1 h), the reaction had proceeded to completion, and was quenched by the slow addition of ice water (500 g). Gas formation from the quench was controlled by adjusting the stirring speed, as decomposition was largely a function of the mixing of the two immiscible layers. Gas effluent was passed through a 20% sodium hydroxide trap, until all gas evolution had ceased (about 3 h). The aqueous layer was removed, and was then extracted with an additional 300 mL of dichloromethane. The organic extracts were combined, dried over MgSO4, and the solvent was removed. Clean product was readily isolated as a viscous, pink oil, which gradually formed a pale pink solid upon seeding with crystals. LCMS m/z (%)=250.0 [M+H]+; 1H NMR (CDCl3, 400 MHz) δ 7.00-7.07 (m, 1H), 7.10 (d, J=9.6 Hz, 1H), 7.15 (d, J=8.1 Hz, 1H), 7.35 (d, J=7.7 Hz, 2H), 7.35-7.41 (m, 2H), 7.42-7.48 (m, 2H).

1. additionInitial addition
2. customresulted in a temperature spike to 25° C. after the first 10 mL
3. additionhad been added over 10 min
4. additionThe addition
5. customa reaction temperature of 5-10° C.
6. temperaturewas maintained
7. additionAfter addition
8. custom(about 1 h)
9. customwas quenched by the slow addition of ice water (500 g)
10. additionmixing of the two immiscible layers
11. customGas effluent was passed through a 20% sodium hydroxide trap, until all gas evolution
12. custom(about 3 h)
13. customThe aqueous layer was removed
14. extractionwas then extracted with an additional 300 mL of dichloromethane
15. dry with materialdried over MgSO4
16. customthe solvent was removed
17. customClean product was readily isolated as a viscous, pink oil, which
18. customgradually formed a pale pink solid