Iodoethane → 4-Isopropoxy-3-methylbenzaldehyde

Participants

Reaction Conditions

Reaction Steps

A solution of [10-(5-fluoro-3-pyridyl)-8-hydroxy-11-oxa-3-azaspiro[5.5]undec-9-en-3-yl]-(4-isopropoxy-3-methyl-phenyl)methanone (56 mg, 0.13 mmol) in ethanol (4.4 mL) was purged with nitrogen for 5 min and treated with 10% palladium on carbon (13 mg, 0.012 mmol). The mixture was evacuated and put under a hydrogen atmosphere (balloon). The reaction mixture was stirred for 12 h at 25° C. The reaction mixture was evacuated and put under an inert atmosphere and re-charged with 10% palladium on carbon (54 mg, 0.05 mmol). The mixture was evacuated and put under a hydrogen atmosphere (balloon) and stirred for 4 h. The reaction mixture was evacuated and put under an inert atmosphere. The Pd-catalyst was removed via filtration and was washed with ethyl acetate. The filtrate was concentrated to dryness and dissolved in DMF (2.4 mL). The mixture was cooled to 0° C. and treated with 60% NaH (28 mg, 1.19 mmol) and ethyl iodide (95 μL, 1.2 mmol). The reaction mixture was warmed to 25° C. and stirred for 2 h. The reaction mixture was quenched by the addition of methanol and partitioned between water and ethyl acetate. The layers were separated and the aqueous layer was extracted with ethyl acetate (3×50 mL). The combined organics were washed with saturated aqueous sodium chloride, dried over sodium sulfate, filtered, and concentrated under reduced pressure. Purification by reverse phase HPLC (1-100% acetonitrile in water, no modifier) afforded cis-4-ethoxy-2-(5-fluoropyridin-3-yl)-1-oxa-9-azaspiro[5.5]undecan-9-yl)(4-isopropoxy-3-methylphenyl)methanone (68 mg) ESI-MS m/z calc. 470.26, found 471.2 (M+1)+; Retention time: 1.453 minutes (3 min run).

Provenance & Evidence