Reaction equation
[F:1][C:2]([F:17])([F:16])[C:3]1[C:7]2[CH:8]=[CH:9][C:10]([OH:15])=[C:11]([CH2:12][CH2:13][CH3:14])[C:6]=2[O:5][N:4]=1.[Br:18][CH2:19][CH2:20]Br.[OH-].[Na+]>O>[Br:18][CH2:19][CH2:20][O:15][C:10]1[CH:9]=[CH:8][C:7]2[C:3]([C:2]([F:1])([F:16])[F:17])=[N:4][O:5][C:6]=2[C:11]=1[CH2:12][CH2:13][CH3:14]Participants
Procedure
3-Trifluoromethyl-7-propyl-6-hydroxy-benzisoxazole (1 g, 4.1 mmol) prepared in Example 24, 1,2-dibromoethane (3.7 g, 18.3 mmol) and NaOH (6 M aqueous solution, 1 mL, 6.0 mmol) were combined and stirred under reflux for 4.5 h. A second portion of NaOH (6 M aqueous solution, 0.43 mL, 2.6 mmol) was added, and stirring under reflux was continued for 4 h. Upon cooling to rt, water (10 mL) was added and the mixture was extracted with CH2Cl2 (3×). The combined organic phases were washed with NaOH (5 M aqueous solution, 2×) and water (3×). The organic phase was dried over Na2SO4, filtered, and concentrated under reduced pressure. The crude product was purified by silica gel flash chromatography (EtOAc/hexanes (v/v) 1:9) to obtain 550 mg (38%) of the title compound as colorless crystals. 1H NMR (300 MHz, CDCl3): δ 0.99 (t, 3H), 1.72 (dt, 2H), 2.94 (t, 2H), 3.70 (t, 2H), 4.42 (t, 2H), 7.03 (d, 1H), 7.58 (d, 1H).
Workup
- temperatureunder reflux for 4.5 h
- stirringstirring
- temperatureunder reflux
- extractionthe mixture was extracted with CH2Cl2 (3×)
- washThe combined organic phases were washed with NaOH (5 M aqueous solution, 2×) and water (3×)
- dry with materialThe organic phase was dried over Na2SO4
- filtrationfiltered
- concentrationconcentrated under reduced pressure
- customThe crude product was purified by silica gel flash chromatography (EtOAc/hexanes (v/v) 1:9)
Sources & evidence
- ORD record
- ord-f054e48d887a4994b9f04837ac9df6c3
- Source dataset
- uspto-grants-2011_03
- Patent number
- US07906653B2
Linked notes
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