Epichlorohydrin → 3-Benzyl-2-chloromethyl-[1,3]oxazepane

Participants

Reaction Steps

A solution of 3-benzylamino-propan-1-ol (14 g, 88.0 mmol) and epichlorohydrin (81.4 g, 880 mmol) was heated to 40° C. After stirring for 3 h the reaction was cooled and excess epichlorohydrin was removed by evaporation in vacuo. Sulfuric acid (10 mL) was added slowly, then the reaction flask was placed in a preheated oil bath at 150° C. Stirring proceeded for 1 h, then the reaction was allowed to cool to room temperature and quenched with the addition of ice. The mixture was adjusted to a basic pH with 10% aqueous Na2CO3 solution and extracted with EtOAc (3×300 mL). The combined organic layers were dried over anhydrous MgSO4, filtered, and dried under reduced pressure. The resulting residue was purified by flash chromatography (70:28:2 hexanes/CH2Cl2/2M NH4OH aq) to afford 5 g of a light yellow oil.

Provenance & Evidence