Benzyl chloromethyl ether → HCID 71116129, compound

Participants

Reaction Conditions

Reaction Steps

To a solution of methyl 3-{[4-(methyloxy)phenyl]methyl}-2-oxo-1-oxa-3-azaspiro[4.5]decane-7-carboxylate (5.05 g, 15.15 mmol) in THF (38.7 mL) under nitrogen at −78° C. was added sodium bis(trimethylsilyl)amide, (1M in THF, 45.4 mL, 45.4 mmol) over 30 minutes. The reaction mixture was stirred at −78° C. for 1 h. Benzyl chloromethyl ether (7.12 g, 45.4 mmol) was then added. After 1 h, the reaction was quenched slowly with water (5 mL). Saturated aq NaCl (100 mL) was then added and the mixture was extracted with EtOAc (2×125 mL). The combined organic layers were dried over Na2SO4, filtered, and concentrated. The compound was then loaded onto florisil and purified using silica gel chromatography CISCO): 10-25% ethyl acetate/hexanes (30 min), 25% (5 min.), 25-45% (15 min), 45% (5 min), 120 g silica. The product eluted at 45 minutes. Methyl 3-{[4-(methyloxy)phenyl]methyl}-2-oxo-7-{[(phenylmethyl)oxy]methyl}-1-oxa-3-azaspiro[4.5]decane-7-carboxylate was obtained as a light yellow oil (4.62 g, 64% yield) and NMR and LCMS were 95% clean for trans product. MS (m/z) 454.0 (M+H+).

Provenance & Evidence