4-Methoxybenzyl alcohol → 5-Bromo-4-ethoxy-2-((4-methoxybenzyl)oxy)pyridine

HRID 1050107Notes

Reaction equation

[Br:1][C:2]1[C:3]([O:9][CH2:10][CH3:11])=[CH:4][C:5](Cl)=[N:6][CH:7]=1.C([O-])([O-])=O.[Cs+].[Cs+].[CH3:18][O:19][C:20]1[CH:25]=[CH:24][C:23]([CH2:26][OH:27])=[CH:22][CH:21]=1>CN(C=O)C>[Br:1][C:2]1[C:3]([O:9][CH2:10][CH3:11])=[CH:4][C:5]([O:27][CH2:26][C:23]2[CH:24]=[CH:25][C:20]([O:19][CH3:18])=[CH:21][CH:22]=2)=[N:6][CH:7]=1

Participants

Conditions

Temperature: 120 °C

Procedure

A mixture of 5-bromo-2-chloro-4-ethoxypyridine (8 g, 33.8 mmol), Cs2CO3 (33.1 g, 101 mmol) and (4-methoxyphenyl)methanol (5.37 g, 38.9 mmol) in DMF (100 mL) was stirred at 120° C. for 12 h. The mixture was then concentrated. The residue was added to DCM (150 mL). The mixture was filtered and the filtrate was concentrated. The crude material was purified by silica column chromatography (PE/EA=8:1). All fractions found to contain product by TLC (PE/EA=5:1, Rf=0.4) were combined and concentrated to yield a yellow solid of 5-bromo-4-ethoxy-2-((4-methoxybenzyl)oxy)pyridine (5 g, 12.57 mmol, 37% yield): 1H NMR (400 MHz, CDCl3) δ: 8.05 (s, 1H), 7.32 (d, J=8.8 Hz, 1H), 6.84 (d, J=8.4 Hz, 1H), 6.17 (s, 1H), 5.18 (s, 2H), 4.02 (q, J=6.8 Hz, 2H), 3.74 (s, 3H), 1.40 (t, J=7.2 Hz, 3H); ES-LCMS m/z 338 (M+H).

Workup

concentrationThe mixture was then concentrated
additionThe residue was added to DCM (150 mL)
filtrationThe mixture was filtered
concentrationthe filtrate was concentrated
customThe crude material was purified by silica column chromatography (PE/EA=8:1)
concentrationconcentrated

Sources & evidence

ORD record: ord-459cb4a2779b44caa609a57b11cadbf5
Source dataset: uspto-grants-2016_07
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US09382238B2

Reaction notes

Loading…