反应详情

2-Phenylacetyl chloride (0.040 ml) was dissolved in acetonitrile (2.0 ml) under a nitrogen atmosphere, and then potassium thiocyanate (60 mg) was added thereto at 50° C., followed by stirring at the same temperature for 3 hrs. The acetonitrile was evaporated under a reduced pressure to give a residue, to which toluene (2.0 ml) and a saturated aqueous solution of sodium hydrogencarbonate (2.0 ml) were added, followed by stirring for 15 min. The toluene layer (0.7 ml) was added to a solution of 4-(4-aminophenoxy)-2-{[4-(pyrrolidin-1-yl)piperidin-1-yl]carbonylamino}pyridine (27 mg) and (S)-(+)-10-camphorsulfonic acid (32 mg) in ethanol (1.0 ml) at room temperature, followed by stirring for 30 min. The reaction mixture was partitioned between ethyl acetate and a saturated aqueous solution of sodium hydrogencarbonate. The organic layer was washed with a saturated aqueous solution of sodium hydrogencarbonate and brine in this order, and dried over anhydrous sodium sulfate. The solvent was evaporated to give a residue, which was then purified by silica gel column chromatography (Fuji Silysia NH, eluent; ethyl acetate). Fractions containing the target compound were concentrated under a reduced pressure to give a residue, which was then dried in vacuum to provide the titled compound (17.2 mg, 44%) as white powder.

1. customat 50° C.
2. customThe acetonitrile was evaporated under a reduced pressure
3. customto give a residue
4. stirringby stirring for 15 min
5. stirringby stirring for 30 min
6. customThe reaction mixture was partitioned between ethyl acetate
7. washThe organic layer was washed with a saturated aqueous solution of sodium hydrogencarbonate and brine in this order
8. dry with materialdried over anhydrous sodium sulfate
9. customThe solvent was evaporated
10. customto give a residue, which
11. customwas then purified by silica gel column chromatography (Fuji Silysia NH, eluent; ethyl acetate)
12. additionFractions containing the target compound
13. concentrationwere concentrated under a reduced pressure
14. customto give a residue, which
15. customwas then dried in vacuum