Sulfuric Acid → 4-(Azetidin-3-yl)morpholine

Participants

Reaction Steps

A solution of 1-azabicyclo[ 1.1.0]butane, prepared from 2,3-dibromopropylamine hydrobromide (58.8 mmol) according to a known procedure described in Tetrahedron Lett. 40: 3761-64 (1999), was slowly added to a solution of morpholine (15.7 ml; 180 mmol) and sulfuric acid (3.3 g of 96% soln.) in anhydrous non-denaturated ethanol (250 ml) at 0° C. The reaction mixture was stirred on ice bath for 30 min., then at room temperature for 8 h. Calcium hydroxide (5.5 g) and 100 ml of water was added and the obtained slurry was stirred for 1 h and then filtered through a pad of cellite. The filtrate was concentrated and distilled at reduced pressure (20 mm Hg) to remove water and an excess of morpholine. The distillation residue was re-distilled at high vacuum using a Kugelrohr apparatus to obtain a pure 4-(azetidin-3-yl)morpholine in 33% yield (2.759 g) as a colorless oily liquid.

Provenance & Evidence