3H-Spiro[2-benzofuran-1,4'-piperidine]

Synthesis

Step 3: 1'-(phenylmethyl)spiro[isophenylurea-1(3H),4'-piperidine] (119 g, 425.9 mmol) was dissolved in ethanol (1 L) and nickel ruanne (12 g) was added and stirred for 1 h at room temperature under argon protection to remove impurities that may poison the catalyst. Subsequently, nickel ruanne was removed by filtration and the filtrate was transferred to a steel autoclave, 10% Pd/C (Degussa Nr. 1835) (12 g) was added, and hydrogenated at 5 bar hydrogen pressure and 40 °C for 19 h. HPLC analysis showed that 2.7% of the starting material remained unreacted. Therefore, the catalyst was removed by filtration and fresh 10% Pd/C (4 g) was added to the filtrate and hydrogenation was continued under the same conditions for 24 h. The catalyst was removed by filtration and the catalyst was added to the filtrate. Upon completion of the reaction, the catalyst was removed by filtration and the ethanol was removed by evaporation to give a light yellow oily substance. The oily substance was co-stirred with heptane (1 L) and spontaneously crystallized to give the white solid product 3H-spiro[2-benzofuran-1,4'-piperidine] (65 g, 80% yield). Mass spectrometry: m/z = 190 [M + H]+.

References

[1] Patent: US2008/171759, 2008, A1. Location in patent: Page/Page column 20
[2] Bioorganic and Medicinal Chemistry, 2009, vol. 17, # 14, p. 5080 - 5095