反应详情

温度

54 °C

Triethylamine (2.2 mL, 0.016 mol) and tert-butyl 2-bromoethylcarbamate (see Preparation R above, 2.83 g, 0.013 mol) were added to a solution of 4-[4-(9-oxa-3,7-diazabicyclo[3.3.1]non-3-yl)butyl]benzonitrile (see Preparation G above, 3.0 g, 0.011 mol) in DMF (50 mL). The mixture was stirred for 24 h at 54° C., cooled to 25° C., and concentrated in vacuo. The residue was dissolved in chloroform and washed with saturated sodium chloride. The aqueous layer was separated and extracted with chloroform (2×150 mL). The combined organic layers were dried (Na2SO4) and concentrated in vacuo. The resulting material was chromatographed on silica gel, eluting first with chloroform:acetonitrile:conc. ammonium hydroxide (9:1:0.02) until the higher Rf impurities were removed. Then the eluent was switched to chloroform:methanol:conc. ammonium hydroxide (9:1:0.02). This afforded 2.76 g (61%) of the title compound.

1. temperaturecooled to 25° C.
2. concentrationconcentrated in vacuo
3. dissolutionThe residue was dissolved in chloroform
4. washwashed with saturated sodium chloride
5. customThe aqueous layer was separated
6. extractionextracted with chloroform (2×150 mL)
7. dry with materialThe combined organic layers were dried (Na2SO4)
8. concentrationconcentrated in vacuo
9. customThe resulting material was chromatographed on silica gel
10. washeluting first with chloroform
11. customammonium hydroxide (9:1:0.02) until the higher Rf impurities were removed