An Efficient Synthesis of N-tert-Butoxycarbonyl-O-cyclohexyl-L-tyrosine

Abstract

A facile and efficient synthesis of N-tert-butoxycarbonyl-O-cyclohexyl-L-tyrosine [Boc-Tyr(Chx)-OH] is described. Boc-Tyr-OH was treated with NaH in dimethylformamide and then with 3-bromocyclohexene to give N-Boc-O-(cyclohex-2-enyl)-L-tyrosine [Boc-Tyr(Che)-OH] in 70% yield. Hydrogenation of Boc-Tyr(Che)-OH over PtO₂ afforded Boc-Tyr(Chx)-OH in almost quantitative yield. The highest yield was achieved when a side product in the synthesis of Boc-Tyr-OH, Boc-Tyr(Boc)-OH, was not removed, because it was also converted to Boc-Tyr(Che)-OH without any additional manipulations. The new synthetic method described here is convenient for practical use, and would facilitate the widespread use of the Chx group for the hydroxy-protection of Tyr.