反应详情

温度

80 °C

A solution of (3R)-6-cyclohexyl-3-[3-(ethoxycarbonyl)-1,2,4-oxadiazol-5-yl]hexanoic acid (Preparation 4) (500 mg, 1.47 mmol) in ethanol (13 ml) was treated with a solution of cyclopropylmethylamine (522 mg, 7.35 mmol) in ethanol (2 ml) and the resulting solution was heated at 80° C. under a nitrogen atmosphere for 10 hours. The solvent was removed under reduced pressure and the residue was dissolved in hydrochloric acid (1M, 10 ml) then extracted with ethyl acetate (×2). The combined organic layers were dried over anhydrous magnesium sulphate, filtered and the solvent removed under reduced pressure. This residue (349 mg) was then dissolved in dichloromethane (15 ml), cooled to 0° C. and treated sequentially with N-methylmorpholine (120 μl, 1.09 mmol) and isobutyl chloroformate (140 μl, 1.09 mmol). This mixture was stirred at 0° C. under a nitrogen atmosphere for 1 hour, then treated with O-(trimethylsilyl)hydroxylamine (140 μl, 1.15 mmol) and stirring continued for 10 minutes at 0° then for 17 hours at room temperature. The mixture was then treated with trifluoroacetic acid:water (5 ml, 9:1) and the solution stirred for 30 minutes. The solvent was removed under reduced pressure and the residue azeotroped from toluene (×2). The residue was purified by HPLCa to afford the title compound as a foam (88 mg).

1. customThe solvent was removed under reduced pressure
2. dissolutionthe residue was dissolved in hydrochloric acid (1M, 10 ml)
3. extractionthen extracted with ethyl acetate (×2)
4. dry with materialThe combined organic layers were dried over anhydrous magnesium sulphate
5. filtrationfiltered
6. customthe solvent removed under reduced pressure
7. dissolutionThis residue (349 mg) was then dissolved in dichloromethane (15 ml)
8. temperaturecooled to 0° C.
9. stirringstirring
10. waitcontinued for 10 minutes at 0°
11. waitfor 17 hours at room temperature
12. customThe solvent was removed under reduced pressure
13. customthe residue azeotroped from toluene (×2)
14. customThe residue was purified by HPLCa