Hydrogen Peroxide → Methyl 3-bromo-4,6-dichloropyridine-2-carboxylate

温度

60 °C

To a stirred solution of methyl 3-bromo-6-chloropyridine-2-carboxylate (1.92 g, 7.67 mmol) in TFA (18 ml) was added hydrogen peroxide (30% w/w aqueous solution, 5.22 ml, 53.7 mmol) and the reaction mixture was heated at 60° C. for 21 h. The reaction mixture was then cooled and slowly poured onto saturated K2CO3 solution (100 ml), followed by extraction of the aqueous layer with EtOAc (3×100 ml), washing of the combined organic phases with brine (2×50 ml), drying (Na2SO4) and evaporation. The desired 3-bromo-6-chloro-2-(methoxycarbonyl)pyridin-1-ium-1-olate (2.61 g, ˜75% purity) was used crude in the next stage of the synthesis without any further purification. To the crude 3-bromo-6-chloro-2-(methoxycarbonyl)pyridin-1-ium-1-olate (˜75% purity, 2.61 g, 7.35 mmol) was added POCl3 (3.42 ml, 36.7 mmol) and the solution was heated to 100° C. for 4 h. After cooling the POCl3 was remove in vacuo to give a white solid which was columned over silica eluting with 0% to 10% of EtOAc in heptane to afford the title compound as a pale yellow powder (1.07 g, 49% over two steps). LC-MS 99%, 2.02 min (3.5 minute LC-MS method), m/z=283.7/285.7/287.7, 1H NMR (500 MHz, Chloroform-d) δ ppm 7.56 (s, 1H) 4.00 (s, 3H).

1. temperatureThe reaction mixture was then cooled
2. extractionfollowed by extraction of the aqueous layer with EtOAc (3×100 ml)
3. washwashing of the combined organic phases with brine (2×50 ml)
4. customdrying
5. custom(Na2SO4) and evaporation
6. customin the next stage of the synthesis
7. customwithout any further purification
8. temperaturethe solution was heated to 100° C. for 4 h
9. customwas remove in vacuo
10. customto give a white solid which

ORDレコード

ord-012d596656c949e7bcc6554d2094b39c

出典データセット

uspto-grants-2016_06

DOI

10.6084/m9.figshare.5104873.v1

特許番号

US09376422B2