反应详情

To a solution of 4-(3-dimethylaminoazetidin-1-yl)piperidine-1-carboxylic acid [4-(4-amino-2-fluorophenoxy)pyridin-2-yl]amide (156 mg) in ethanol (5.0 ml) was added (1S)-(+)-10-camphorsulfonic acid (152 mg), followed by stirring at room temperature for 15 min. A solution of 2-phenylacetyl isothiocyanate in toluene (0.25 M, 4.37 ml) was added to the reaction mixture, followed by stirring at room temperature for 2 hrs. Ethyl acetate (50 ml) and a saturated aqueous solution of sodium hydrogencarbonate (20 ml) were added to the reaction mixture, and the organic layer was separated. The aqueous layer was extracted with ethyl acetate. The combined organic layer was washed with brine, and dried over anhydrous sodium sulfate. The organic layer was concentrated to give a residue, which was then purified by silica gel column chromatography (FUJI Silysia NH, eluent; ethyl acetate, then ethyl acetate:methanol=20:1). Fractions containing a crude product were concentrated to give a residue, to which diethyl ether (5 ml) and hexane (5 ml) were added to give a precipitate. The precipitate was suspended in the solvent. Then the precipitate was filtered off, washed with hexane, and dried under aeration to provide the titled compound (56.6 mg, 25.7%) as pale yellow powder.

1. stirringby stirring at room temperature for 2 hrs
2. customthe organic layer was separated
3. extractionThe aqueous layer was extracted with ethyl acetate
4. washThe combined organic layer was washed with brine
5. dry with materialdried over anhydrous sodium sulfate
6. concentrationThe organic layer was concentrated
7. customto give a residue, which
8. customwas then purified by silica gel column chromatography (FUJI Silysia NH, eluent
9. additionFractions containing a crude product
10. concentrationwere concentrated
11. customto give a residue
12. customto give a precipitate
13. filtrationThen the precipitate was filtered off
14. washwashed with hexane
15. customdried under aeration