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

Participants

Reaction Steps

14.8 g (200 millimoles) of t-butanol and 29 ml of ethyl acetate were added to a reaction system followed by blowing in 9.9 g (100 millimoles) of phosgene. A mixed solution containing 5.48 g (50.7 millimoles) of 2-amino-6-picoline, 12.5 g (97.0 millimoles) of N,N-diisopropylethylamine and 32 mL of ethyl acetate was dropped into this solution over the course of 1.5 hours while holding the internal temperature at −15° C. to −5° C. Following completion of dropping, the solution was stirred for 1 hour. Next, 50 mL of water and 5.1 g of 28% sodium hydroxide were sequentially added while holding the internal temperature at 0° C. or lower. After separating the liquid, the aqueous phase was extracted with ethyl acetate. The organic phases were combined and mixed, and a portion of the organic phase was sampled and subjected to quantitative analysis by HPLC. The target (6-methyl-pyridin-2-yl)-carbamic acid tert-butyl ester was obtained at a yield of 89%. The yield of 1,3-bis-(6-methyl-pyridin-2-yl)-urea (urea compound) was 8%. Furthermore, the yield of the urea compound was based on the raw material 2-amino-6-picoline and was calculated using 2 molecules of 2-amino-6-picoline for 1 molecule of the urea compound (and was similarly calculated in the subsequent examples and comparative examples).

Provenance & Evidence