Methanol → 5-Bromo-2-(2-chlorophenylamino)-3,4-difluorobenzoic acid methyl ester
Reaction equation
[Br:1][C:2]1[C:3]([F:20])=[C:4]([F:19])[C:5]([NH:11][C:12]2[CH:17]=[CH:16][CH:15]=[CH:14][C:13]=2[Cl:18])=[C:6]([CH:10]=1)[C:7]([OH:9])=[O:8].S(Cl)(Cl)=O.[CH3:25]O>>[Br:1][C:2]1[C:3]([F:20])=[C:4]([F:19])[C:5]([NH:11][C:12]2[CH:17]=[CH:16][CH:15]=[CH:14][C:13]=2[Cl:18])=[C:6]([CH:10]=1)[C:7]([O:9][CH3:25])=[O:8]Participants
Conditions
- Temperature
- 85 °C
Procedure
To a solution of 5-bromo-3,4-difluoro-2-((2-chlorophenyl)amino)benzoic acid (25.63 g, 70.69 mmol) in MeOH (300 mL) was added thionyl chloride (20 mL). The resulting solution was stirred at 85° C. overnight. Most MeOH was removed in vacuo. The residue was neutralized with saturated sodium bicarbonate (aq.) and extracted with ethyl acetate (100 mL×3). The combined organic layer was washed with water (100 mL) and brine (100 mL) sequentially, dried over Na2SO4, filtered and concentrated. After purification by column chromatography on silica gel (petroleum ether/ethyl acetate, 50:1, v/v), the corresponding product was obtained as a white solid (22.84 g, 85.8% yield). 1H NMR (400 MHz, CDCl3): δ 9.15 (s, 1H), 8.06 (m, 1H), 7.41 (m, 1H), 7.24 (m, 1H), 7.00 (m, 1H), 6.91 (m, 1H), 3.95 (s, 3H).
Workup
- customMost MeOH was removed in vacuo
- extractionextracted with ethyl acetate (100 mL×3)
- washThe combined organic layer was washed with water (100 mL) and brine (100 mL) sequentially
- dry with materialdried over Na2SO4
- filtrationfiltered
- concentrationconcentrated
- customAfter purification by column chromatography on silica gel (petroleum ether/ethyl acetate, 50:1, v/v)
Sources & evidence
- ORD record
- ord-3098c12b619f42f6b80077c7b622b190
- Source dataset
- uspto-grants-2016_03
- Patent number
- US09290468B2
Reaction notes
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