Sodium Hydroxide → 5-Bromo-2-methoxypyridine

A solution of bromine (13.1mL, 256.6 mMol) in glacial acetic acid (45 mL) was added drop wise into a mechanically stirred suspension of 2-Methoxy-pyridine (19 mL, 183 mMol) in glacial acetic acid (88 mL) with the temperature kept at ten degrees. After complete addition the solution was allowed to stir overnight while gradually warming to room temperature. Upon arrival the reaction mixture was poured over ice and the pH adjusted to eight with solid sodium hydroxide. The material was then diluted with diethyl ether (150 mL) and filtered thru Celite. The aqueous layer was extracted with diethyl ether (2×100 mL) and ethyl acetate (2×100 mL) and all the organics combined. The solution was dried with magnesium sulfate, filtered, and concentrated on a rotary evaporator to a dark brown oil. The oil was eluted thru a plug of silica gel with hexanes and concentrated to yield 22.6 g (66% yield) of 5-Bromo-2-methoxy-pyridine as a clear oil. 1H NMR (DMSO-d6): δ=8.29 (dd,1H,J=2.6,0.5 Hz), 7.89 (dd, 1H, J=8.8, 2,6 Hz), 6.84 (dd, 1H, J=8.8, 0.5 Hz), 3.84 (s, 3H). LC/MS (Method A), rt=1.35 mins., purity=76.5%, calculated mass=187,[M+H]+=188/190, [M−H]− 187/189. HPLC (Method C): rt=8.1 mins., purity=88.0% @ 210-370 nm and 88.3% @ 286 nm.

1. customkept at ten degrees
2. additionAfter complete addition the solution
3. additionUpon arrival the reaction mixture was poured over ice
4. filtrationfiltered
5. extractionThe aqueous layer was extracted with diethyl ether (2×100 mL) and ethyl acetate (2×100 mL) and all the
6. dry with materialThe solution was dried with magnesium sulfate
7. filtrationfiltered
8. concentrationconcentrated on a rotary evaporator to a dark brown oil
9. washThe oil was eluted
10. concentrationconcentrated

ORD record

ord-81b5b8d6399d4780a460e9431806b812

Source dataset

uspto-grants-2010_04

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US07696210B2