Dimethylformamide → Methyl 5-bromo-2-methoxy-3-methylbenzoate

HRID 391444Notes

Reaction equation

[Br:1][C:2]1[CH:3]=[C:4]([CH3:12])[C:5](O)=[C:6]([CH:10]=1)[C:7]([OH:9])=[O:8].IC.[C:15](=O)([O-])[O-].[K+].[K+].CN(C)[CH:23]=[O:24]>>[Br:1][C:2]1[CH:3]=[C:4]([CH3:12])[C:5]([O:24][CH3:23])=[C:6]([CH:10]=1)[C:7]([O:9][CH3:15])=[O:8]

Participants

Reactant 4

HCID 6228Dimethylformamide

HCID 6328Methyl iodide

HCID 11430Potassium Carbonate

HCID 27643455-Bromo-2-hydroxy-3-methylbenzoic acid

Product 1

HCID 2764346Methyl 5-bromo-2-methoxy-3-methylbenzoate

Procedure

5-Bromo-2-hydroxy-3-methylbenzoic acid (2.8 g, 12.1 mmol), iodomethane (1.97 mL, 31.6 mmol) and potassium carbonate (16.9 g, 123 mmol) were combined in dimethylformamide (30 mL). After stirring at room temperature for 16 h, the solvent was removed in vacuo and the crude product dissolved in ethyl acetate, which was washed with water (2×), then brine (2×), dried over sodium sulfate, and concentrated. Flash chromatography on silica gel (10% ethyl acetate/hexanes) gave 2.26 g (72%). 1H-NMR (CDCl3, 500 MHz) δ 7.74-7.75 (m, 1H), 7.45-7.46 (m, 1H), 3.90 (s, 3H), 3.80 (s, 3H), 2.28 (s, 3H). Mass spec.: 261.08 (MH)+.

Workup

customthe solvent was removed in vacuo
dissolutionthe crude product dissolved in ethyl acetate
washwhich was washed with water (2×)
dry with materialbrine (2×), dried over sodium sulfate
concentrationconcentrated
customFlash chromatography on silica gel (10% ethyl acetate/hexanes) gave 2.26 g (72%)

Sources & evidence

ORD record: ord-58d7d8776e6f4666b6f7cc8c7a2dad2f
Source dataset: uspto-grants-2013_02
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US08383821B2

Reaction notes

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