تفاعل #410527
ord-d89fd8746f344cdc9a54815184619c2f
معادلة التفاعل
المتفاعلات
ظروف التفاعل
المعالجة
- 1درجة الحرارةCool in an ice bath
- 2درجة الحرارةHeat to reflux
- 3workup.WAITAfter 18 hours
- 4درجة الحرارةcool
- 5درجة الحرارةagain heat to reflux
- 6workup.WAITAfter 24 hours
- 7درجة الحرارةcool in a dry-ice/acetone bath
- 8درجة الحرارةWarm to ambient temperature
- 9تركيزConcentrate in vacuo
- 10أخرىto remove most to the tetrahydrofuran
- 11استخلاصextract three times with ethyl acetate
- 12استخلاصExtract the combined organic layers with water
- 13تجفيفbrine, dry the organic layer over Na2SO4
- 14ترشيحfilter
- 15أخرىevaporate in vacuo
- 16أخرىto give a residue
الإجراء التجريبي
Combine (1H-benzimidazol-2-yl)(1-(t-butoxycarbonyl)piperidin-4-yl)amine (3.5 mmol) and tetrahydrofuran (45 mL) and dimethylformamide (5 mL). Cool in an ice bath and add sodium hydride (0.21 g, 60% in oil, 5.22 mmol). After 1 hour, add 5-chloropentan-2-one, ethylene ketal (0.79 mL, 5.22 mmol) and tetra-n-butylammonium bromide (112 mg, 0.35 mmol) and warm to ambient temperature. Heat to reflux. After 18 hours, cool, add sodium hydride (0.1 g) and 5-chloropentan-2-one, ethylene ketal (0.50 mL) and again heat to reflux. After 24 hours, cool in a dry-ice/acetone bath and add a saturated aqueous solution of ammonium chloride. Warm to ambient temperature and dilute the reaction mixture with a saturated aqueous solution of sodium bicarbonate. Concentrate in vacuo to remove most to the tetrahydrofuran and extract three times with ethyl acetate. Extract the combined organic layers with water and then brine, dry the organic layer over Na2SO4, filter, and evaporate in vacuo to give a residue. Chromatograph the residue on silica gel eluting with 5% methanol/dichloromethane/0.1% saturated aqueous ammonia solution to give (1-(4-oxopentyl)-1H-benzimidazol-2-yl)(1-(t-butoxycarbonyl)piperidin-4-yl)amine, ethylene ketal.