1-Fluoronaphthalene → (S)-(+)-N,N-Dimethyl-3-(1-naphthalenyloxy)-3-(2-thienyl)propanamine

Participants

Reaction Steps

A 1.60 g portion of (S)-(-)-N,N-dimethyl-3-hydroxy-3-(2-thienyl)propanamine was dissolved in 8 ml of dimethylsulfoxide at ambient temperature, to which was added 0.35 g of sodium hydride as a 60% dispersion in mineral oil with vigorous stirring. After 30 minutes of stirring, 0.28 g of potassium benzoate was added, and stirring was continued for 10 minutes more. Then 1.52 g of 1-fluoronaphthalene was added and the mixture was then stirred at 50° C. for 8 hours. The reaction mixture was poured slowly into 30 ml of cold water, and the pH was adjusted to 4.8 by addition of acetic acid. Fifteen ml of hexane was added, the mixture was stirred for 10 minutes, and the layers were separated. The aqueous phase was stirred again with 15 ml of hexane and the phases separated. The pH of the aqueous phase was adjusted to 12.5 by addition of aqueous sodium hydroxide, and 15 ml of ethyl acetate was added. The basic mixture was stirred at ambient temperature for 10 minutes, and the layers were separated. The aqueous phase was extracted with another 15 ml portion of ethyl acetate, and the organic extracts were combined, washed once with 30 ml of water, and dried over magnesium sulfate. The solvent was removed under vacuum to obtain a red-brown oil which was dissolved in the minimal amount of 1:1 ethyl acetate:hexane. The solution was flushed through a pad of silica gel using as eluant, ethyl acetate:hexane:methanol:amonium hydroxide, 47:47:5.8:0.2. The product fraction was evaporated under vacuum to obtain 2.3 g of the desired product as an amber oil.

Provenance & Evidence