94994-25-9

General procedure for the synthesis of methyl 4-formylbicyclo[2.2.2]octane-1-carboxylate from methyl 4-(hydroxymethyl)bicyclo[2.2.2]octane-1-carboxylate: Intermediate A51L: methyl 4-formylbicyclo[2.2.2]octane-1-carboxylate To a solution of Intermediate A511 (540 mg, 2.72 mmol) in dichloromethane (20 mL) was added Dess-Martin periodinane (1502 mg, 3.54 mmol). The reaction mixture was stirred at room temperature overnight. Upon completion of the reaction, the mixture was cooled to 0 °C and the reaction was carefully quenched with saturated sodium bicarbonate solution. The organic and aqueous layers were separated. The aqueous layer was extracted with dichloromethane. The organic layers were combined, washed with saturated brine, dried over anhydrous sodium sulfate and filtered. The filtrate was concentrated to give the crude product. The residue was purified by silica gel column chromatography (40 g REDISEP column with 10-50% ethyl acetate in hexane solution as eluent). The fraction containing the target product was collected and the solvent was evaporated to give the intermediate A51L (400 mg, 74.8% yield). Mass spectrum (electrospray ionization): m/z = 199 [M + H]+;. 1H NMR (400 MHz, chloroform-d) δ ppm 9.48 (s, 1H), 3.68 (s, 3H), 1.94-1.78 (m, 6H), 1.78-1.61 (m, 6H).

[1] Tetrahedron Letters, 1999, vol. 40, # 4, p. 781 - 784
[2] Patent: US9273058, 2016, B2. Location in patent: Page/Page column 534
[3] Journal of Labelled Compounds and Radiopharmaceuticals, 2007, vol. 50, # 4, p. 219 - 223
[4] Journal of Organic Chemistry, 1985, vol. 50, # 7, p. 1079 - 1087