5-Bromo-3-methoxy-2-methylpyridine

As shown in step 6-iv of Scheme 6, Compound 1020 (5 g, 18.73 mmol) was dissolved in dry THF (94 mL) and Pd(PPhAs shown in step 6-iv of Scheme 6, Compound 1020 (5 g, 18.73 mmol) was dissolved in dry THF (94 mL) and Pd(PPh[00111] As shown in step 6-iv of Scheme 6, Compound 1020 (5 g, 18.73 mmol) was dissolved in dry THF (94 mL) and Pd(PPh3)4 (2.16 g, 1.873 mmol) was added. The reaction mixture was cooled in an ice bath, and methylmagnesium bromide in 3/1 THF/toluene (17.4 mL, 1.4 M, 24.35 mmol) was slowly added. The ice bath was removed, and the reaction was heated to reflux. The reaction was stirred at reflux for 1 h and 3 mL of the methylmagnesium bromide solution were added. The reaction was stirred at reflux for another 20 min and 2 mL of the methylmagnesium bromide solution were added. The reaction was stirred at reflux for 1 h and cooled to RT. Ethyl ether and 1 N HCl were added, and the organic layer was separated and washed with 1 N HCl. The aqueous extracts were washed with ethyl ether three times. The aqueous layer was made basic with 2 N NaOH and extracted with ethyl acetate three times. The ethyl acetate extracts were combined and dried over Na2SO4, then concentrated under reduced pressure. The residue was purified via silica gel chromatography (0-25% ethyl acetate/hexanes) to afford 5-bromo-3-methoxy-2-methylpyridine (Compound 1021, 2.7 g, 71% yield): ESMS (M+H) 202, 204. 5-Bromo-2-ethyl-3-methoxypyridine was made by an analogous procedure: ESMS (M+H) 216, 218; IH NMR (CDCl3) delta 8.2 (d, IH), 7.2 (d, IH), 3.8 (s, 3H), 2.8 (q, 2H), 1.2 (t, 3H).As shown in step 6-iv of Scheme 6, Compound 1020 (5 g, 18.73 mmol) was dissolved in dry THF (94 mL) and Pd(PPh3)4 (2.16 g, 1.873 mmol) was added. The reaction mixture was cooled in an ice bath, and methylmagnesium bromide in 3/1 THF/toluene (17.4 mL, 1.4 M, 24.35 mmol) was slowly added. The ice bath was removed, and the reaction was heated to reflux. The reaction was stirred at reflux for 1 h and 3 mL of the methylmagnesium bromide solution were added. The reaction was stirred at reflux for another 20 min and 2 mL of the methylmagnesium bromide solution were added. The reaction was stirred at reflux for 1 h and cooled to RT. Ethyl ether and 1 N HCl were added, and the organic layer was separated and washed with 1 N HCl. The aqueous extracts were washed with ethyl ether three times. The aqueous layer was made basic with 2 N NaOH and extracted with ethyl acetate three times. The ethyl acetate extracts were combined and dried over Na2SO4, then concentrated under reduced pressure. The residue was purified via silica gel chromatography (0-25% ethyl acetate/hexanes) to afford 5-bromo-3-methoxy-2-methylpyridine (Compound 1021, 2.7 g, 71% yield): ESMS (M+H) 202, 204.

Molecular Weight:202.05
XLogP3:1.9
Hydrogen Bond Acceptor Count:2
Rotatable Bond Count:1
Exact Mass:200.97893
Monoisotopic Mass:200.97893
Topological Polar Surface Area:22.1
Heavy Atom Count:10
Complexity:110
Covalently-Bonded Unit Count:1
Compound Is Canonicalized:Yes