[Synthesis]
Preparation of 5.7: Tert-butyl 4-(2-ethoxy-2-oxoethyl)spiro[chromane-2,4'-piperidine]-1'-carboxylate (5.6, 2.0 g, 5.1 mmol) was dissolved in a solvent mixture of methanol (30 mL), tetrahydrofuran (30 mL) and water (30 mL). To this solution was added lithium hydroxide monohydrate (1.35 g, 32 mmol). The reaction mixture was stirred overnight at room temperature. Upon completion of the reaction, the mixture was concentrated under vacuum to remove the organic solvent. The aqueous phase was washed with ether to remove non-polar impurities. Subsequently, the aqueous layer was acidified with 1N HCl to pH about 4 and extracted with dichloromethane. The organic extracts were combined, dried over anhydrous sodium sulfate, filtered and concentrated in vacuum to afford the target product 2-(1'-(tert-butoxycarbonyl)spiro[chroman-2,4'-piperidin]-4-yl)acetic acid (5.7). Yield: 100%. 1H NMR (400 MHz, DMSO-d6) δ: 7.26 (m, 1H), 7.10 (m, 1H), 6.86 (m, 1H), 6.90 (m, 1H), 3.75 (m, 1H), 3.63 (m, 1H), 3.22 (m, 2H), 2.93 (m, 2H), 2.32 (dd, 1H) , 2.0 (m, 1H), 2.68-2.52 (m, 4H), 1.40 (s + m, 10H). |