反应详情

HATU (2.267 g) was added in one portion to a solution of 5-methylthiophene-2-carboxylic acid (0.652 g) and 2-benzhydryl-5-oxa-2,8-diazaspiro[3.5]nonane (example 33, step f) (1.35 g) and triethylamine (1.917 mL) in DMF (20 mL) at 0° C. The cooling bath was removed and the mixture stirred at room temperature for 2 hours. The mixture was partitioned between ethyl acetate and brine, the organic layer was washed twice with brine before being dried over sodium sulphate, filtered and the solvent removed under reduced pressure. The crude product was purified by flash silica chromatography, elution gradient 0.4 to 5% methanol in dichloromethane. Pure fractions were evaporated to dryness to afford the subtitled compound. Yield 1.5 g.

1. customThe cooling bath was removed
2. customThe mixture was partitioned between ethyl acetate and brine
3. washthe organic layer was washed twice with brine
4. dry with materialbefore being dried over sodium sulphate
5. filtrationfiltered
6. customthe solvent removed under reduced pressure
7. customThe crude product was purified by flash silica chromatography, elution gradient 0.4 to 5% methanol in dichloromethane
8. customPure fractions were evaporated to dryness