3,4-Dichlorophenol → 3-(3,4-Dichlorophenoxy)-1-(diphenylmethyl)azetidine

Participants

Reaction Steps

A mixture of 48 g (0.2 mole) of 1-(diphenylmethyl)-3-azetidinol and 22 g (0.22 mole) of triethylamine in 800 mL of toluene was stirred in a tap water bath while 27.5 g (0.22 mole) of methanesulfonyl chloride was added dropwise and stirring was continued for 18 h. The reaction mixture was treated with 400 mL of isopropyl ether then filtered. The filter cake was washed with 2×150 mL of 50/50 isopropyl ether and toluene. The combined filtrates were treated with 32.6 g (0.2 mole) of 3,4-dichlorophenol, 100 mg of tetra-n-butylammonium bromide and 24 g (0.6 mole) of sodium hydroxide in 100 mL of water. This mixture was stirred vigorously at reflux for 16 h. The basic aqueous portion was separated and the organic portion washed with water, dried over magnesium sulfate then concentrated to a solid residue, 74.5 g. Several recrystallizations from ethanol-water gave a product which was contaminated with starting azetidinol. Therefore, the material (57.4 g) was dissolved in toluene and treated with silica gel. After stirring for 6 h, the silica gel was removed by filtration and washed with 50/50 ethyl acetate and toluene. The filtrates were concentrated to yield 45.9 g (59.7%) of pure product. A sample for elemental analysis was recrystallized from 190 ethanol, mp. 114°-115° C.

Provenance & Evidence