تفاعل #4940

معادلة التفاعل

2-(2-chloroethyl)-2,3-dihydro-4-methylpyrido[3,2-f]-1,4-oxazepin-5-(4H)-one hydrochloride

sodium hydroxide

4-[bis(4-fluorophenyl)-methyl]piperidine

→

2-[2-[4-[Bis(4-fluorophenyl)methyl]-1-piperidinyl]ethyl]-2,3-dihydro-4-methylpyrido[3,2-f][1,4]oxazepin-5(4H)-one dihydrochloride hemihydrate

المذيبات

chloroform

ظروف التفاعل

المعالجة

1. 1
   تجفيفThe chloroform was dried over sodium sulfate
2. 2
   تركيزconcentrated on the rotary evaporator
3. 3
   workup.DISSOLUTIONThe residue was dissolved in 50 ml of ethanol
4. 4
   درجة الحرارةThe solution was heated
5. 5
   درجة الحرارةto reflux for 18 hr
6. 6
   تركيزconcentrated on the rotary evaporator
7. 7
   أخرىThe residue was partitioned between dilute sodium hydroxide and chloroform
8. 8
   تجفيفThe chloroform was dried over anhydrous sodium sulfate
9. 9
   تركيزconcentrated
10. 10
    أخرىThe residue was chromatographed on a Waters 500 HPlC (silica/92% ethyl acetate-8% triethylamine)
11. 11
    workup.DISSOLUTIONAfter concentration of the desired product, the residue was dissolved in isopropyl alcohol
12. 12
    workup.ADDITIONtreated with ethereal hydrogen chloride

الإجراء التجريبي

Ten grams (0.036 mole) of 2-(2-chloroethyl)-2,3-dihydro-4-methylpyrido[3,2-f]-1,4-oxazepin-5-(4H)-one hydrochloride were partitioned between dilute sodium hydroxide and chloroform. The chloroform was dried over sodium sulfate and concentrated on the rotary evaporator. The residue was dissolved in 50 ml of ethanol and 10.3 g (0.036 mole) of 4-[bis(4-fluorophenyl)-methyl]piperidine was added. The solution was heated to reflux for 18 hr and concentrated on the rotary evaporator. The residue was partitioned between dilute sodium hydroxide and chloroform. The chloroform was dried over anhydrous sodium sulfate and concentrated. The residue was chromatographed on a Waters 500 HPlC (silica/92% ethyl acetate-8% triethylamine). After concentration of the desired product, the residue was dissolved in isopropyl alcohol and treated with ethereal hydrogen chloride. The resulting crystals weighed 3 g (14%) and melted at 160°-180° C.

المصدر