Pyridine → Benzyl (2,4-difluorophenyl)carbamate

To 2,4-difluoro-phenylamine (1, 50.00 g, 0.39 mol) were added 550 mL of anhydrous dichloromethane, and anhydrous pyridine (61.27 g, 0.77 mol), followed by addition of benzyl chloroformate (2, 79.28 g, 0.46 mol) dropwise while maintaining the temperature at <30° C. The reaction mixture was stirred at room temperature for 2 hours and an additional 6.61 g (0.04 mol) of benzyl chloroformate was added and the reaction stirred an additional 2 hours, followed by addition of another 6.61 g of benzyl chloroformate. The reaction mixture was stirred overnight at room temperature, then concentrated under reduced pressure and diluted with 250 mL of water. The pH was adjusted to 2 with 2 M aqueous hydrochloric acid, then extracted with 3×250 mL of ethyl acetate. The organic layers were combined and dried over magnesium sulfate, filtered and the filtrate concentrated under vacuum. The residue was slurried in hexane, filtered and the solid collected and dried to provide the desired compound (24, 78.6 g, 77%).

1. temperaturewhile maintaining the temperature at <30° C
2. stirringthe reaction stirred an additional 2 hours
3. stirringThe reaction mixture was stirred overnight at room temperature
4. concentrationconcentrated under reduced pressure
5. additiondiluted with 250 mL of water
6. extractionextracted with 3×250 mL of ethyl acetate
7. dry with materialdried over magnesium sulfate
8. filtrationfiltered
9. concentrationthe filtrate concentrated under vacuum
10. filtrationfiltered
11. customthe solid collected
12. customdried

ORD record

ord-94055e0ab36e437baea4506d586ceb26

Source dataset

uspto-grants-2014_12

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US08901301B2