Reaktion #4940

Reaktionsgleichung

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

Lösungsmittel

chloroform

Reaktionsbedingungen

Aufarbeitung

1. 1
   TrocknenThe chloroform was dried over sodium sulfate
2. 2
   Einengenconcentrated on the rotary evaporator
3. 3
   workup.DISSOLUTIONThe residue was dissolved in 50 ml of ethanol
4. 4
   TemperaturThe solution was heated
5. 5
   Temperaturto reflux for 18 hr
6. 6
   Einengenconcentrated on the rotary evaporator
7. 7
   SonstigeThe residue was partitioned between dilute sodium hydroxide and chloroform
8. 8
   TrocknenThe chloroform was dried over anhydrous sodium sulfate
9. 9
   Einengenconcentrated
10. 10
    SonstigeThe 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

Vorschrift

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.

Quelle