2-Chloroethyl methyl ether → 5-Bromo-N-(2-methoxyethyl)pyridin-2-amine

Temperature

2.5 °C

5-Bromo-pyridin-2-ylamine (29-1, 1.43 g, 8.27 mmol) was dissolved in anhydrous DMF (20 mL) under N2. The solution was cooled to 0-5° C. and added with NaH (>1.0 equiv) until no hydrogen was formed. The solution was added with 1-chloro-2-methoxy-ethane (2.5 ml, 14 mmol) dropwisely at 0-5° C. The reaction mixture was stirred at 0° C. for 50 min. The solution was quenched with methanol and saturated aqueous NH4Cl. The solution was concentrated under reduced pressure and distributed between water, brine, and dichloromethane. The aqueous phase was then extracted with dichloromethane and the combined organic phases were dried over sodium sulfate, filtered, and concentrated. The residue was purified by flash column chromatography on silica gel to give 5-bromo-N-(2-methoxyethyl)pyridin-2-amine (29-2, 1.01 g) as brown solids in 53% yield: 1H NMR (500 MHz, CDCl3) δ 8.01 (d, 1 H), 7.57 (d, 1 H), 6.57 (d, 1 H), 3.97 (t, 2 H), 3.49 (t, 2 H), 3.35 (s, 3 H). ESI-MS: m/z 231.0 (M+H)+.

1. customwas formed
2. customThe solution was quenched with methanol and saturated aqueous NH4Cl
3. concentrationThe solution was concentrated under reduced pressure
4. extractionThe aqueous phase was then extracted with dichloromethane
5. dry with materialthe combined organic phases were dried over sodium sulfate
6. filtrationfiltered
7. concentrationconcentrated
8. customThe residue was purified by flash column chromatography on silica gel

ORD record

ord-8e3af1f7c8f4435e9863647f2172b513

Source dataset

uspto-grants-2015_04

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US08999983B2