Phosgene → tert-Butyl (6-(chloromethyl)pyridin-2-yl)carbamate

Participants

Reaction Steps

5.61 g (75.7 millimoles) of t-butanol and 22 mL of ethyl acetate were added to a reaction system followed by blowing in 3.8 g (38.4 millimoles) of phosgene. A mixed solution containing 1.95 g (13.7 millimoles) of 2-amino-6-chloromethylpyridine, 4.86 g (37.6 millimoles) of N,N-diisopropylethylamine and 19 mL of ethyl acetate were dropped into this solution over the course of 1 hour while holding the internal temperature at −15° C. to −5° C. Following completion of dropping, the solution was stirred for 1 hour. Next, water and 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. A portion of the organic phase was sampled and subjected to quantitative analysis by HPLC. The target (6-chloromethyl-pyridin-2-yl)-carbamic acid tert-butyl ester was obtained at yield of 74%. The yield of 1,3-bis-(6-chloromethyl-pyridin-2-yl)-urea (urea compound) was 10%.

Provenance & Evidence