Practical Synthesis ofp‐Aminophenethylspiperone (NAPS), a High‐Affinity, Selective D2‐Dopamine Receptor Antagonist

Abstract Because attempts to scale up the published synthetic preparation of p‐aminophenethylspiperone (NAPS) by N‐alkylation of spiperone with 4‐nitrophenethyl bromide followed by reduction gave poor yields and difficulties during purification, an alternative synthetic approach has been developed. Use of 4‐(N‐tert‐butyloxycarbonyl) aminophenethyl bromide to alkylate spiperone followed by the Boc group deprotection gave NAPS in 56% yield. This procedure provides an improved and efficient synthesis of the important high‐affinity, selective D2‐dopamine receptor antagonist NAPS.