Sodium Hydroxide → 3-(3-(Piperidin-1-ylmethyl)phenoxy)propan-1-amine

Participants

Reaction Conditions

Reaction Steps

3-Chloropropylamine hydrochloride (VI) (0.2 mol, 39 g) was dissolved into 3N sodium hydroxide solution (containing 10% sodium chloride) and extracted with 300 ml of benzene. The benzene layer was dried over anhydrous magnesium sulfate. Separately, 3-piperidinomethylphenol (V) (0.2 mol, 38.2 g), sodium hydroxide (0.25 mol, 10 g), 100 ml of dimethylsulfoxide, and 70 ml of benzene were charged to a flask equipped with a water quantitative measurement tube, and heated at 130° C. for 3 hours while stirring to remove water produced by the tube, followed by continued stirring for 2 hours at 140°-150° C. To the resulting reaction mixture was dropwise added said benzene solution of 3-chloropropylamine at 150° C. while stirring over 4 hours. The reaction mixture was allowed to stand still to cool to room temperature to separate deposited sodium chloride by filtration. The filtrate was concentrated under reduced pressure and vacuum distilled to obtain 42.7 g of N-[3-(3-aminopropoxy)benzyl] piperidine (VII) (yield: 86.0%). m.p. 148°-151° C./0.25 mmHg.

Provenance & Evidence