Sodium Hydroxide → 5-Bromo-3-ethoxy-2-methoxypyridine

To a stirred mixture of 3-ethoxy-2-methoxy-pyridine (2.7 g, 17.6 mmol, 1.0 equiv) and sodium acetate (1.74 g, 21.2 mmol, 1.2 equiv) in acetic acid (50 mL) at 10° C. was slowly added a solution of bromine (1.09 mL, 3.38 g, 21.2 mmol, 1.2 equiv) in acetic acid (10 mL). After the addition was completed the reaction mixture was stirred for 1 h at rt. The reaction mixture was poured on ice, neutralized with NaOH and the solution extracted with diethylether (3×50 mL). The combined organic phases were dried over MgSO4 and the solvent removed by evaporation under reduced pressure yielding 3.86 g (94%) of a mixture of 5-bromo-3-ethoxy-2-methoxy-pyridine and 6-bromo-3-ethoxy-2-methoxy-pyridine in the ratio 3:2 as indicated by 1H NMR, which was used directly in the next reaction step. 1H NMR (300 MHz, CDCl3): δ 1.39 (t, J=7.0 Hz, 3H), 3.91 (s, 3H), 3.98 (q, J=7.0 Hz, 2H), 7.05 (d, J=1.9 Hz, 1H), 7.69 (d, J=1.9 Hz, 1H).

1. additionAfter the addition
2. additionThe reaction mixture was poured on ice
3. extractionthe solution extracted with diethylether (3×50 mL)
4. dry with materialThe combined organic phases were dried over MgSO4
5. customthe solvent removed by evaporation under reduced pressure

ORD record

ord-6e8be6f4bd2c4190b7aa9942046b63cc

Source dataset

uspto-grants-2010_01

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US07645753B2