反应详情

温度

0 °C

A solution of tert-butyl 1-oxa-4,9-diazaspiro[5.5]undecane-9-carboxylate hydrochloride (WuXi PharmaTech) (0.594 g) and 2-(trifluoromethyl)thiazole-4-carboxylic acid (0.4 g) in DMF (10 mL) was treated with triethylamine (0.848 mL) and cooled to 0° C. HATU (1.003 g) was added and the mixture stirred at 20° C. for 2 hours. The mixture was partitioned between ethyl acetate and brine, the organic layer was washed twice with brine, dried over sodium sulphate, filtered and the solvent evaporated under reduced pressure. The crude product was purified by flash silica chromatography eluting with 40% ethyl acetate in isohexane to yield the product as the free base. This was dissolved in dichloromethane (40 mL) and treated with trifluoroacetic acid (10 mL) and then the mixture was allowed to stand at 20° C. for 1 hour. Toluene (60 mL) was added and the solvent removed under reduced pressure to afford the subtitled compound. Yield 0.740 g.

1. customThe mixture was partitioned between ethyl acetate and brine
2. washthe organic layer was washed twice with brine
3. dry with materialdried over sodium sulphate
4. filtrationfiltered
5. customthe solvent evaporated under reduced pressure
6. customThe crude product was purified by flash silica chromatography
7. washeluting with 40% ethyl acetate in isohexane
8. customto yield the product as the free base
9. waitto stand at 20° C. for 1 hour
10. customthe solvent removed under reduced pressure