Methyl iodide → Methyl 4-methoxybicyclo[2.2.2]octane-1-carboxylate

Temperature

60 °C

To a solution of methyl 4-hydroxybicyclo[2.2.2]octane-1-carboxylate (8.9 g, 48 mmol) in anhydrous THF (150 mL) at −78° C. was added n-butyl lithium (23 mL, 57.5 mmol, 2.5 M solution in hexane) over 30 min, followed by the slow addition of iodomethane (14 g, 98 mmol). The mixture was stirred at 60° C. for 3 h and quenched by addition of saturated aqueous ammonium chloride solution (50 mL). The resulting solution was concentrated and the residue was extracted with ethyl acetate (150 mL×2). The organic layers were combined and washed with brine, dried over magnesium sulfate and then concentrated. The residue was purified by silica gel column chromatography (10% ethyl acetate in petroleum ether) to give the title product (6.5 g, 67%). 1H NMR (400 MHz, CDCl3) δ ppm 3.64 (s, 3H), 3.18 (s, 3H), 1.95-1.89 (m, 6H), 1.70-1.65 (m. 6H).

1. customquenched by addition of saturated aqueous ammonium chloride solution (50 mL)
2. concentrationThe resulting solution was concentrated
3. extractionthe residue was extracted with ethyl acetate (150 mL×2)
4. washwashed with brine
5. dry with materialdried over magnesium sulfate
6. concentrationconcentrated
7. customThe residue was purified by silica gel column chromatography (10% ethyl acetate in petroleum ether)

ORD record

ord-8027376b494f4b42b907f8383aee1670

Source dataset

uspto-grants-2015_09

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US09139534B2