反应详情

LiAlH4 (150 mg, 3.95 mmol) was poured some more to a solution of intermediate 36, 3-{[4-(methylsulfonyl)piperazin-1-yl]carbonyl}cyclobutanone (500 mg, 1.92 mol) in absolute THF (5 mL) in argon under stirring. The mixture was refluxed under stirring for 4 h, cooled, and 10 N NaOH (0.5 mL) and water (0.5 mL) were added. The organic layer was decanted, and the water layer was extracted with THF (2×5 mL). The residue was vacuum-dried and dissolved in CH2Cl2 (10 mL). Triethylamine (0.550 mL, 4 mmol) was added, and then methanesulphonyl chloride (0.163 mL, 2.11 mmol) was added in argon under stirring at 0° C. The mixture was stirred at room temperature for 20 h, and the saturated NaHCO3 solution (5 mL) was added. The layers were separated, and the water layer was extracted with chloroform (2×5 mL). The organic layers were dried over Na2SO4, evaporated, and the residue was diluted on SiO2 ((10 g, 40-63 μm, CHCl3/hexane 8:2, 9:1, 9.5:0.5→CHCl3→CHCl3/MeOH 99:1→90:10) to give compound 7 as white crystals in 70% (435 mg) yield. 1H-NMR data (dmso-d6): 4.84 (qw, 1H, J=7.6 Hz), 3.12 (s, 3H), 3.07 (m, 4H), 2.85 (s, 3H), 2.54 (d, 1H, J=9.5 Hz), 2.4-2.50 (m, 7H), 2.00-2.1 (m, 1H), 1.8-1.9 (m, 2H).

1. temperatureThe mixture was refluxed
2. stirringunder stirring for 4 h
3. temperaturecooled
4. customThe organic layer was decanted
5. extractionthe water layer was extracted with THF (2×5 mL)
6. customThe residue was vacuum-dried
7. dissolutiondissolved in CH2Cl2 (10 mL)
8. stirringunder stirring at 0° C
9. stirringThe mixture was stirred at room temperature for 20 h
10. customThe layers were separated
11. extractionthe water layer was extracted with chloroform (2×5 mL)
12. dry with materialThe organic layers were dried over Na2SO4
13. customevaporated
14. additionthe residue was diluted on SiO2 ((10 g, 40-63 μm, CHCl3/hexane 8:2, 9:1, 9.5:0.5→CHCl3→CHCl3/MeOH 99:1→90:10)