3-[[4-(TERT-BUTOXYCARBONYL)PIPERAZIN-1-YL]METHYL]BENZOIC ACID synthesis

Yield:500013-38-7 74%

Reaction Conditions:

Stage #1: 4-(3-(methoxycarbonyl)benzyl)-1-Boc-piperazinewith lithium hydroxide in tetrahydrofuran;water at 20; for 24 h;
Stage #2: with potassium hydrogensulfate in tetrahydrofuran;water; pH=5;

Steps:

18.B 18B: tert-Butyl 4-(3-carboxybenzyl)piperazine-1-carboxylate

Lithium hydroxide monohydrate (339 mg, 9.27 mmol) was added to a solution of tert-butyl 4-(3-(methyloxycarbonyl)benzyl)piperazine-1-carboxylate (1.55 g, 4.63 mmol) in THF (10 ml) and water (2 ml). The solution was stirred at room temperature for 24 h then acidified to pH 5 with 0.3 M KHSO4 and extracted successively with chloroform and dichloromethane. The combined extracts were concentrated in vacuo to give a white solid identified as tert-butyl 4-(3-carboxybenzyl)piperazine-1-carboxylate (1.09 g, 74%).

References:

EP1449844,2004,A1 Location in patent:Page 31