A.
Ethyl 3-(1-azetidinyl)propionate. A solution of
150 g. (2.00 moles) of 3-amino-1-propanol in
500 g. (5.00 moles) of ethyl acrylate (Note
1) is refluxed for 2 hours in a
1-l., round-bottomed flask. Subsequent vacuum removal of the excess
ethyl acrylate at steam temperature yields
548 g.. (
99%) of crude
diethyl 3-N-(3-hydroxypropyl)iminodipropionate. A stirred, cooled solution of this material (548 g.) in
1 l. of chloroform and
10 ml. of N,N-dimethylformamide is treated dropwise with
262 g. 2.20 moles) of thionyl chloride. By cooling with an
ice bath and controlling the addition rate, the reaction temperature is maintained below 40° (Note
2). After the addition is complete, the reaction mixture is stirred for 30 minutes at room temperature and poured slowly into a slurry of
340 g. of sodium hydrogen carbonate in 1 l. of water (Note
3). The organic layer is separated (Note
4) and dried over
sodium sulfate, and the solvent is removed under reduced pressure, below 50°, yielding
570 g. (
97%) of crude
diethyl 3-N-(3-chloropropyl)iminodipropionate. A mixture of 100 g. of this crude material,
200 g. of anhydrous, powdered sodium carbonate (Note
5), and
10.0 g. of pentaerythritol (Note
6) in
200 ml. of diethyl phthalate is placed in a
500-ml., round-bottomed flask fitted with a
vacuum-distillation head and an
effective stirrer. The system is evacuated through a
trap of sufficient capacity to contain 50 ml. of liquid, and the product is distilled by heating the stirred suspension with a heating mantle at 10–15 mm. By proper adjustment of the heat source, the distillation temperature is maintained below 150°, minimizing codistillation of
diethyl phthalate. The distillate is collected until the head temperature cannot be kept below 150°. Redistillation of the resulting crude product through a
4-in. Vigreux column yields
34.0 g. (
57–68%) of
ethyl 3-(1-azetidinyl)propionate, b.p. 86–87° (12 mm.), 99% pure by GC (Note
7).