反应详情

温度

80 °C

A mixture of 9-(5-{3-chloro-4-[(1-methylethyl)oxy]phenyl}-1,2,4-oxadiazol-3-yl)-2,3,4,5-tetrahydro-1,4-benzoxazepine hydrochloride (Example 31) (20 g, 47.4 mmol), potassium carbonate (16.4 g, 118 mmol) and potassium iodide (7.86 g, 47.4 mmol) in N,N-dimethylformamide (DMF) (250 ml) was treated with ethyl 4-bromobutanoate (7.46 ml, 52.1 mmol) and the resulting mixture stirred at 80° C. under nitrogen for 180 minutes. The mixture was allowed to cool and poured into water (1000 ml). The resulting precipitate was extracted into ethyl acetate (3×250 ml) and the extracts combined, washed with water (2×250 ml), then brine (150 ml), dried (sodium sulphate) and evaporated to give a colourless viscous oil. The crude material was purified by chromatography on silica, eluting with a 20-100% gradient of ethyl acetate in isohexane to give the title compound as a colourless, viscous oil which crystallised on standing (18.3 g).

1. temperatureto cool
2. extractionThe resulting precipitate was extracted into ethyl acetate (3×250 ml)
3. washwashed with water (2×250 ml)
4. dry with materialbrine (150 ml), dried (sodium sulphate)
5. customevaporated
6. customto give a colourless viscous oil
7. customThe crude material was purified by chromatography on silica
8. washeluting with a 20-100% gradient of ethyl acetate in isohexane