Methanol → Methyl 3,5-dimethoxy-4-methylbenzoate
Reaction equation
S(=O)(=O)(O)O.[CH3:6][C:7]1[C:15]([O:16][CH3:17])=[CH:14][C:10]([C:11]([OH:13])=[O:12])=[CH:9][C:8]=1[O:18][CH3:19].[CH3:20]O>>[CH3:6][C:7]1[C:8]([O:18][CH3:19])=[CH:9][C:10]([C:11]([O:13][CH3:20])=[O:12])=[CH:14][C:15]=1[O:16][CH3:17]Participants
Procedure
Concentrated sulphuric acid (1 mL), was added dropwise to a solution of 4-methyl-3,5-dimethoxybenzoic acid (186) (5.01 g, 25.56 mmol) in refluxing methanol (20 mL). The reaction mixture was heated at reflux for a further 5 hours and then cooled to room temperature and concentrated to a third of its original volume. The concentrate was poured onto crushed ice (c. 150 mL) and allowed to stand for 30 minutes. The aqueous mixture was extracted with ethyl acetate (3×100 mL) and the combined organic phase washed with distilled water (3×100 mL), brine (2×100 mL) and dried over anhydrous MgSO4. Removal of excess solvent under reduced pressure afforded the product as a beige solid (187) (4.865 g, 23.17 mmol, 91%); 1H NMR (270 MHz, CDCl3) δ 7.21 (s, 2H), 3.91 (s, 3H), 3.86 (s, 6H), 2.13 (s, 3H); 13C NMR (67.8 MHz, CDCl3) δ 171.57, 167.28, 158.16, 158.10, 128.23, 120.39, 105.20, 104.70, 55.85, 52.13, 8.77, 8.66.
Workup
- temperatureThe reaction mixture was heated
- temperatureat reflux for a further 5 hours
- concentrationconcentrated to a third of its original volume
- additionThe concentrate was poured
- customonto crushed ice (c. 150 mL)
- extractionThe aqueous mixture was extracted with ethyl acetate (3×100 mL)
- washthe combined organic phase washed with distilled water (3×100 mL), brine (2×100 mL)
- dry with materialdried over anhydrous MgSO4
- customRemoval of excess solvent under reduced pressure
Sources & evidence
- ORD record
- ord-891381be79d34d7d9db29972ff72b67b
- Source dataset
- uspto-grants-2006_05
- Patent number
- US07049311B1
Reaction notes
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