Reaction #4959

Reaction equation

azetidine

ammonium hydroxide

azetidine

7-chloro-2-(2-chloroethyl)-2,3-dihydro-4-methylpyrido[3,2-f][1,4]-oxazepine-5(4H)-one

potassium carbonate

azetidine

→

2-[2-(1-Azetidinyl)ethyl]-7-chloro-2,3-dihydro-4-methylpyrido[3,2-f][1,4]-oxazepin-5(4H)-one oxalate

Solvents

water

methanol

ethyl acetate

dimethyl sulfoxide

Conditions

Workup

1. 1
   workup.STIRRINGthe mixture stirred for 24 hr more
2. 2
   Extractionextracted with 4×100 ml of benzene
3. 3
   Washwashed with 3×100 ml of water
4. 4
   Dryingdried over sodium sulfate
5. 5
   Filtrationfiltered
6. 6
   Concentrationconcentrated by rotary evaporation
7. 7
   workup.ADDITIONThe syrupy residue was treated with oxalic acid in isopropyl alcohol

Procedure

To a solution of 6 g (0.022 mole) of 7-chloro-2-(2-chloroethyl)-2,3-dihydro-4-methylpyrido[3,2-f][1,4]-oxazepine-5(4H)-one in 40 ml of dimethyl sulfoxide was added 8.0 g of crushed potassium carbonate and 1.5 g (0.026 mole) of azetidine. The reaction was stirred at room temperature for 24 hr. After checking ty TLC [7:2:1 by volume ethyl acetate:methanol:conc. ammonium hydroxide, another 0.4 g (0.007 mole) of azetidine was added. Two days later, another 0.5 g (0.0087 mole) of azetidine was added and the mixture stirred for 24 hr more. The reaction mixture was diluted with 100 ml of water and extracted with 4×100 ml of benzene. The organic extracts were combined, washed with 3×100 ml of water, dried over sodium sulfate, filtered, and concentrated by rotary evaporation. The syrupy residue was treated with oxalic acid in isopropyl alcohol. This yielded 4.2 g (56.5%) of white material, m.p. 169°-174° C. with decomposition.

Source