Tetrahydrofuran → [2-(2,5-Difluorobenzylthio)phenyl]acetic acid
Reaction equation
[S:1]1[C:5](=[O:6])[CH2:4][C:3]2[CH:7]=[CH:8][CH:9]=[CH:10][C:2]1=2.[F:11][C:12]1[CH:19]=[CH:18][C:17]([F:20])=[CH:16][C:13]=1[CH2:14]Br.[O:21]1CCCC1>>[F:11][C:12]1[CH:19]=[CH:18][C:17]([F:20])=[CH:16][C:13]=1[CH2:14][S:1][C:2]1[CH:10]=[CH:9][CH:8]=[CH:7][C:3]=1[CH2:4][C:5]([OH:21])=[O:6]Participants
Procedure
A mixture of benzo[b]thiophen-2(3H)-one (11.2 g) aqueous sodium hydroxide (5.58 g in 100 ml water) and tetrahydrofuran (10 ml) was heated under reflux for two hours. A solution of 2,5-difluorobenzyl bromide (15.5 g) in tetrahydrofuran (10 ml) was added and the mixture refluxed for a further 2 hours and allowed to cool. The aqueous layer was clarified by ether extraction and then acidified with concentrated hydrochloric acid. The precipitate was collected, washed with water and dried. The solid was recrystallised from dipropyl ether/hexane to give [2-(2,5-difluorobenzylthio)phenyl]acetic acid, mp 106.5°-107.5°. A solution of this product (14.4 g) in methanol (150 ml) containing concentrated sulphuric acid (0.5 ml) was heated under reflux for 4 hours, cooled and evaporated. The residue was dissolved in ethyl acetate/ether and washed with water and aqueous sodium bicarbonate, dried and evaporated to give methyl [2-(2,5-difluorobenzylthio)phenyl]acetate, as a light brown oil.
Workup
- temperaturewas heated
- temperatureunder reflux for two hours
- temperaturethe mixture refluxed for a further 2 hours
- temperatureto cool
- extractionThe aqueous layer was clarified by ether extraction
- customThe precipitate was collected
- washwashed with water
- customdried
- customThe solid was recrystallised from dipropyl ether/hexane
Sources & evidence
- ORD record
- ord-a43cf7bd732046d19876d5b00aa6b74d
- Source dataset
- uspto-grants-1993_11
- Patent number
- US05264609
Reaction notes
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