反应详情

3-Pyrrolidin-1-yl-oxetane-3-carbonitrile (intermediate A, 1.6 g, 91% purity, 10 mmol) was dissolved in 10 mL tetrahydrofurane. Phenyllithium (2M in dibutylether, 9.8 mL, 20 mmol) was added dropwise at −5° C. The reaction mixture was stirred at room temperature for 1.5 hours and poured into cold saturated sodium bicarbonate solution. The mixture was extracted three times with ethyl acetate. The combined organic phases were dried on sodium sulfate, filtered and evaporated. The residue was dissolved in 35 mL methanol and sodiumborohydride (0.77 g, 20 mmol) was added portion-wise at 0° C. The reaction mixture was stirred at room temperature for 2 hours and quenched by addition of water. The solvent was evaporated off. The residue was taken up in water and ethyl acetate and was extracted three times with ethyl acetate. The combined organic phases were dried on sodium sulfate, filtered and evaporated. The crude product (brown oil, 2.26 g, 99%) was used for the next step without further purification, MS: m/e=216.3 [(M−NH2)+].

1. extractionThe mixture was extracted three times with ethyl acetate
2. customThe combined organic phases were dried on sodium sulfate
3. filtrationfiltered
4. customevaporated
5. dissolutionThe residue was dissolved in 35 mL methanol
6. stirringThe reaction mixture was stirred at room temperature for 2 hours
7. customquenched by addition of water
8. customThe solvent was evaporated off
9. extractionethyl acetate and was extracted three times with ethyl acetate
10. customThe combined organic phases were dried on sodium sulfate
11. filtrationfiltered
12. customevaporated
13. customThe crude product (brown oil, 2.26 g, 99%) was used for the next step without further purification, MS