4-Methoxybenzyl alcohol → 3-Benzyloxy-6-iodo-2-(4-methoxybenzyloxy)pyridine

HRID 625967

Reaction equation

[CH3:1][O:2][C:3]1[CH:4]=[CH:5][C:6]([CH2:9][OH:10])=[CH:7][CH:8]=1.[H-].[Na+].[H][H].[CH2:15]([O:22][C:23]1[C:24](Br)=[N:25][C:26]([I:29])=[CH:27][CH:28]=1)[C:16]1[CH:21]=[CH:20][CH:19]=[CH:18][CH:17]=1>CN(C=O)C.O>[CH2:15]([O:22][C:23]1[C:24]([O:10][CH2:9][C:6]2[CH:7]=[CH:8][C:3]([O:2][CH3:1])=[CH:4][CH:5]=2)=[N:25][C:26]([I:29])=[CH:27][CH:28]=1)[C:16]1[CH:17]=[CH:18][CH:19]=[CH:20][CH:21]=1

Participants

Conditions

Temperature: 100 °C

Procedure

To a 0° C. solution of p-methoxybenzyl alcohol (13.83 g, 100 mmol) in 33 mL DMF was added sodium hydride (4 g, 100 mmol) slowly. The mixture was stirred at room temperature until evolution of hydrogen had ceased, and crude 3-(benzyloxy)-2-bromo-6-iodopyridine (13.01 g, 33.4 mmol) was added. The resulting solution was heated to 100° C. for 1 h under nitrogen. After cooling, the mixture was diluted with water and extracted with ethyl acetate. The aqueous layer was removed and discarded. The organic layer was collected, dried over anhydrous magnesium sulfate and purified by silica gel chromatography to afford 3-(benzyloxy)-6-iodo-2-[(4-methoxybenzyl)oxy]pyridine (12.1 g, 27.1 mmol, 81% yield). ES-MS (M+H)+=448.

Workup

temperatureAfter cooling
extractionextracted with ethyl acetate
customThe aqueous layer was removed
customThe organic layer was collected
dry with materialdried over anhydrous magnesium sulfate
custompurified by silica gel chromatography

Sources & evidence

ORD record: ord-f9eb8841c74a40c78695c720eed21e84
Source dataset: uspto-grants-2016_04
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US09309199B2

Linked notes

Loading…