o-Xylyl bromide → Methyl 3-hydroxy-5-{[(2-methylphenyl)methyl]oxy}benzoate

HRID 1510296Notes

Reaction equation

[OH:1][C:2]1[CH:3]=[C:4]([CH:9]=[C:10]([OH:12])[CH:11]=1)[C:5]([O:7][CH3:8])=[O:6].[H-].[Na+].[CH3:15][C:16]1[CH:23]=[CH:22][CH:21]=[CH:20][C:17]=1[CH2:18]Br>CN(C=O)C>[CH3:8][O:7][C:5](=[O:6])[C:4]1[CH:3]=[C:2]([O:1][CH2:15][C:16]2[CH:23]=[CH:22][CH:21]=[CH:20][C:17]=2[CH3:18])[CH:11]=[C:10]([OH:12])[CH:9]=1

Participants

Conditions

Temperature: 15 °C

Procedure

To a solution of methyl 3,5-dihydroxybenzoate (50 g, 0.30 mol) in DMF (500 ml) at 0° C. was added sodium hydride (10.8 g, 0.27 mol) portion wise. The reaction was allowed to warm to 15° C., and stirred for 20 minutes. The mixture was re-cooled to 0° C. and a solution of 2-methylbenzyl bromide (36 ml, 0.27 mol) in DMF (50 ml) was added over 30 minutes. The reaction was warmed to ambient temperature and concentrated in vacuo. The residual oil was partitioned between ethyl acetate (500 ml) and water (250 ml), and the ethyl acetate layer was separated, washed with water and evaporated. The residue was purified by column chromatograph on silica gel (gradient, 0-100% ethyl acetate in isohexane) to give the desired compound (21.9 g, 27%).

Workup

temperatureThe mixture was re-cooled to 0° C.
temperatureThe reaction was warmed to ambient temperature
concentrationconcentrated in vacuo
customThe residual oil was partitioned between ethyl acetate (500 ml) and water (250 ml)
customthe ethyl acetate layer was separated
washwashed with water
customevaporated
customThe residue was purified by column chromatograph on silica gel (gradient, 0-100% ethyl acetate in isohexane)

Sources & evidence

ORD record: ord-f9fbe2bf7b5c41cdaea60aa1b50f6fa8
Source dataset: uspto-grants-2012_07
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US08211925B2

Reaction notes

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