Ethanol → HCID 59371503, compound

Participants

Reaction Conditions

Reaction Steps

In a 50 mL round-bottom flask with magnetic stirrer, N-[3-[3-[5-[[1-(tert-butoxycarbonyl)-2(S)-azetidinyl]methoxy]-3-pyridyl]phenyl]propyl]-3,4,5,6-tetrachlorophthalimide (347 mg, 522 μmol) was dissolved in acetonitrile (2 mL), tetrahydrofuran (1 mL), and ethanol (1 mL). Ethylenediamine (157 μL, 2.35 mmol, 4.5 equiv.) was added. The flask was equipped with a reflux condenser, three-way stopcock, and Ar balloon, and the atmosphere was exchanged. The mixture was heated in an oil bath at 60° C. for 160 min. The resulting yellowish solution and fine, colorless precipitate were cooled to room temperature. TLC (SiO2, CH2Cl2/MeOH/Et3N 90:10:5, UV detection) demonstrated disappearance of the starting material which was replaced with two major new spots (Rf approx. 0.5 and 0.4) besides nonpolar byproducts. The mixture was evaporated and the residue chromatographed on SiO2 (23×2.5 cm, CH2Cl2/MeOH/Et3N 93:7:5, then 9:1:1). Fractions containing the two major products were combined, evaporated, and dried (50° C./oil pump vacuum) to yield 358 mg of crude 3-[3-[5-[[1-(tert-butoxycarbonyl)-2(S)-azetidinyl]methoxy]-3-pyridyl]phenyl]propanamine as a yellowish, turbid glass, which was used in the subsequent step without purification.

Provenance & Evidence