Chloroacetonitrile → 2-[(5-Bromopyridin-3-yl)oxy]acetonitrile

温度

0 °C

A dry, 250 mL one neck round bottom flask was charged with 3-bromo-5-hydroxypyridine 3 (4.9470 g, 28.4 mmol), 40 mL dry ACN, cesium carbonate (CS2CO3) (3.41 ml, 42.6 mmol) and a stirbar. The flask was fitted with an Ar inlet, and cooled to 0° C. To the solution was added 2-chloroacetonitrile (2.34 ml, 37.0 mmol) dissolved in 10 mL dry ACN over 15 minutes via an addition funnel. The reaction warmed to room temperature overnight. The slurry was filtered through a 0.22 μm PTFE filter membrane, and concentrated under a stream of nitrogen. The residue was loaded onto 100 g of SiO2 wet-packed with ACN, and eluted with 500 mL ACN. The eluent was concentrated in vacuo, and the residue was sublimed at 0.5 mm Hg in a 90° C. oil bath to afford 2-(5-bromopyridin-3-yloxy)acetonitrile (3.49 g, 57.6% yield). 1H NMR (300 MHz, MeOH) δ ppm 5.12 (s, 2H) 7.81 (dd, J=2.63, 1.83 Hz, 1H) 8.35 (d, J=2.63 Hz, 1H) 8.38 (dd, J=1.83, 0.29 Hz, 1H). 13C NMR (75 MHz, MeOH) δ ppm 55.24 (s, 1 C) 116.18 (s, 1 C) 121.90 (s, 1 C) 126.59 (s, 1 C) 137.86 (s, 1 C) 145.61 (s, 1 C) 155.29 (s, 1 C). HPLC-MS: retention time=1.42 min (99.0%@215 nm; 98.9% @254 nm; m/z=212.8, calculated for C7H579Br2N2O+H+=213.0, m/z=214.8, calculated for C7H581Br2N2O+H+=215.0).

1. customThe flask was fitted with an Ar inlet
2. temperatureThe reaction warmed to room temperature overnight
3. filtrationThe slurry was filtered through a 0.22 μm PTFE
4. filtrationfilter membrane
5. concentrationconcentrated under a stream of nitrogen
6. washeluted with 500 mL ACN
7. concentrationThe eluent was concentrated in vacuo
8. customwas sublimed at 0.5 mm Hg in a 90° C.

ORDレコード

ord-5e8087244e1e4796bb3a963a42d5a70e

出典データセット

uspto-grants-2011_04

DOI

10.6084/m9.figshare.5104873.v1

特許番号

US07928140B2