N-Boc-1-[4-spiro-piperidine]-3-indanone

Synthesis

Tert-butyl 3-hydroxyspiro[indene-1,4'-piperidine]-1'-carboxylate (20 g, 66 mmol) was used as a raw material, which was dissolved in ethyl acetate (300 mL) and o-iodobenzoic acid (IBX) (37 g, 132 mmol) was added with stirring. The reaction mixture was heated to 80 °C for 12 hours. After completion of the reaction, the mixture was cooled to room temperature and the solid was separated by filtration. The filter cake was washed well with ethyl acetate (3 x 100 mL). The filtrate and washings were combined and concentrated under reduced pressure to give a solid residue. The residue was purified by silica gel column chromatography, first eluting with a 1:10 solvent mixture of ethyl acetate-hexane, and then switching to a 1:3 solvent mixture of ethyl acetate-hexane, to give 1'-(tert-butoxycarbonyl)-spiro-(indene-1,4'-piperidinium) (19.5 g, 98% yield) as a white solid with a melting point of 121 °C. The residue was purified by IR (KBr). The product was characterized by IR (KBr), 1H NMR (CDCl3,400 MHz), 13C NMR (CDCl3,100 MHz) and GC-MS (EI) to confirm its structure.

References

[1] Patent: WO2008/68159, 2008, A1. Location in patent: Page/Page column 28; 30
[2] Bioorganic and Medicinal Chemistry Letters, 2012, vol. 22, # 1, p. 363 - 366
[3] Patent: WO2009/61681, 2009, A2. Location in patent: Page/Page column 65