反应详情

To a stirred solution of 1-tert-butyl-5-trifluoromethyl-1H-pyrazole-4-carboxylic acid (2.334 g; 9.88 mmol) in N,N-dimethylformamide/methylene chloride (1:4 ratio, 15 mL) at room temperature was added diisopropylethylamine (9.00 mL; 51.13 mmol). TSTU (5.420 g; 18.0 mmol) was then added. The resulting mixture was allowed to stir at room temperature for 2 hr and then 2-adamantylamine (1.654 g; 9.89 mmol) was added. The mixture was allowed to stir over night at room temperature and then concentrated in vacuo. The residue was partitioned between ethyl acetate and water. The organic layer was washed sequentially with 0.5N HCl, saturated sodium bicarbonate then brine, dried over sodium sulfate, filtered and concentrated in vacuo to give the crude product as a light brown solid. Purification by column chromatography (RediSep-120 g silica gel, 10%—100% ethyl acetate/hexanes) provided the desired trans-isomer of 1-tert-butyl-5-trifluoromethyl-1H-pyrazole-4-carboxylic acid (5-hydroxy-adamantan-2-yl)-amide (1.23 g, 32%) as a white solid. by resulting light yellow gum was triturated with diethyl ether to provide 1-tert-butyl-5-chloro-1H-pyrazole-4-carboxylic acid adamantan-2-ylamide (4.02 g, 80%) as a white powder. The cis-isomer was also isolated (1.58 g, 41%).

1. stirringto stir over night at room temperature
2. concentrationconcentrated in vacuo
3. customThe residue was partitioned between ethyl acetate and water
4. washThe organic layer was washed sequentially with 0.5N HCl, saturated sodium bicarbonate
5. dry with materialbrine, dried over sodium sulfate
6. filtrationfiltered
7. concentrationconcentrated in vacuo
8. customto give the crude product as a light brown solid
9. customPurification by column chromatography (RediSep-120 g silica gel, 10%—100% ethyl acetate/hexanes)