Phosgene → tert-Butyl (6-methylpyridin-2-yl)carbamate

Temperature

-15 °C

462 ml of ethyl acetate were added to a reaction system and cooled to −15° C. followed by blowing in 114.4 g (1.16 moles) of phosgene over the course of 1.8 hours. A mixed solution containing 50.2 g (0.462 moles) a of 2-amino-6-picoline, 131.8 g (1.02 moles) of N,N-diisopropylethylamine, 85.7 g (1.16 moles) of t-butanol and 231 mL of ethyl acetate was then dropped into this phosgene solution over the course of 2.8 hours while holding the internal temperature at −15° C. to 0° C. Following completion of dropping, the solution was stirred for 1.7 hours. Next, 300 mL of water and 200 mL of 28% sodium hydroxide were sequentially added while holding the internal temperature at 0° C. or lower. The aqueous phase was extracted with 300 mL of ethyl acetate. The organic phases were combined and mixed and then concentrated under reduced pressure. A mixed solution of methanol and water was added to the resulting crude product. The precipitated crystals were then subjected to suction filtration and dried under reduced pressure to obtain 93.4 g of the target (6-methyl-pyridin-2-yl)-carbamic acid tert-butyl ester (yield: 94%). The yield of 1,3-bis-(6-methyl-pyridin-2-yl)-urea (urea compound) was 3%.

1. customat −15° C. to 0° C
2. customat 0° C.
3. extractionThe aqueous phase was extracted with 300 mL of ethyl acetate
4. additionmixed
5. concentrationconcentrated under reduced pressure
6. additionA mixed solution of methanol and water was added to the resulting crude product
7. filtrationThe precipitated crystals were then subjected to suction filtration
8. customdried under reduced pressure

ORD record

ord-110e3594db304cc6a71d31c4fe434298

Source dataset

uspto-grants-2014_02

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US08653269B2