反应详情

To a solution of 8.94 g (19.9 mmol) (2S,4R)-[6-(4-hydroxy-2-hydroxymethyl-pyrrolidin-1-yl)-4-iodo-pyridin-3-yl]-methyl-carbamic acid tert-butyl ester in 85 ml dichloromethane were added 50 ml of a 2 M solution of hydrogen chloride in diethylether at 0° C. The reaction mixture was stirred at room temperature for 22 h and concentrated in vacuo. The residue was re-dissolved in 85 ml dichloromethane and treated with 17 ml (99.4 mmol) N-ethyldiisopropylamine. At 0° C. 19.0 g (59.7 mmol) 2-(3,5-bis-trifluoromethyl-phenyl)-2-methyl-propionyl chloride were added dropwise. The reaction mixture was stirred at room temperature for 4 h and concentrated in vacuo. After addition of 250 ml methanol and 70 ml 3 N potassium hydroxide solution the mixture was stirred at room temperature for 2 h. The mixture was concentrated to remove methanol and extracted with four 750 ml-portions of dichloromethane. The combined organic layers were washed with 500 ml 1 N sodium hydroxide solution and 500 ml brine, dried over sodium sulfate and evaporated. Flash-chromatography gave 11 g (87%) of the title compound as a light yellow foam.

1. concentrationconcentrated in vacuo
2. dissolutionThe residue was re-dissolved in 85 ml dichloromethane
3. customAt 0° C
4. stirringThe reaction mixture was stirred at room temperature for 4 h
5. concentrationconcentrated in vacuo
6. additionAfter addition of 250 ml methanol and 70 ml 3 N potassium hydroxide solution the mixture
7. stirringwas stirred at room temperature for 2 h
8. concentrationThe mixture was concentrated
9. customto remove methanol
10. extractionextracted with four 750 ml-portions of dichloromethane
11. washThe combined organic layers were washed with 500 ml 1 N sodium hydroxide solution and 500 ml brine
12. dry with materialdried over sodium sulfate
13. customevaporated