Methyl iodide → Tert-butyl 4-(3-methoxy-4-(methoxycarbonyl)phenoxy)piperidine-1-carboxylate

Participants

Reaction Steps

To a solution of methyl 4-(N-t-butoxycarbonyl-4-piperidinyloxy)-2-hydroxybenzoate (50 g, 0.14 mol) from Step 4 above and iodomethane (17.4 mL, 0.28 mol) in DMF (300 mL) at 0° C. was added NaH (6.55 g of a 60% suspension in mineral oil, 0.164 mol) in several portions over a period of 2 h. The resulting suspension was warmed to ambient temperature and stirred for 18 h. The mixture was quenched with methanol (5 mL) and concentrated under reduced pressure. The residue was suspended in EtOAc (500 mL) and washed with water (2×250 mL) and brine (250 mL). The EtOAc layer was dried (MgSO4), filtered, and concentrated under reduced pressure. The crude product was purified by pressurized silica gel column chromatography using a gradient elution of 20-40% EtOAc-hexane. Methyl 4-(N-t-butoxycarbonyl-4-piperidinyloxy)-2-methoxybenzoate was obtained as a gum that solidified on standing (TLC: Rf = 0.25 (3:1 hexane:EtOAc); HPLC (method A) retention time= 9.72 min).

Provenance & Evidence