Morpholine → HCID 68959039, compound

Participants

Reaction Conditions

Reaction Steps

A solution consisting of morpholine (7.5 mL) in THF (100 mL) is cooled to 0° C. (ice/salt bath) and a solution of methylmagnesium bromide (55 mL of a 1.4 M solution in toluene/THF 3:1 v/v) is added by addition funnel while the temperature is maintained between 0 and 5° C. (over 15 minutes.) The orange reaction mixture is stirred at 0° C. for 30 minutes and subsequently a mixture consisting of 1-{3-[4-(tert-butyl-dimethyl-silanyloxy)-phenyl]-4-phenyl-isoxazol-5-yl}-cyclopropanecarboxylic acid methyl ester (12.8 g) in THF (50 mL) is added by addition funnel over 5 minutes. The flask is removed from the ice bath. The reaction mixture is cooled to 0° C. and a solution consisting of methylmagnesium bromide (55 mL of a 1.4 M solution in toluene/THF 3:1 v/v) is added over 10 minutes. After 20 min further methylmagnesium bromide (55 mL of a 1.4 M solution in toluene/THF 3:1 v/v) is added over 10 minutes. The ice bath is removed and the reaction mixture is allowed to warm to room temperature overnight. The reaction mixture is poured into an ice/ammonium chloride solution. The mixture is twice extracted with ethyl acetate and the combined extracts are dried and concentrated under reduced pressure. The concentrate is purified by flash silica gel column chromatography. Elution with a gradient (1% to 5% ethyl acetate in hexanes) afforded 1-(1-{3-[4-(tert-butyl-dimethyl-silanyloxy)-phenyl]-4-phenyl-isoxazol-5-yl}-cyclopropyl)-ethanone (4.8 g); MS (APCI+) m/z 434 (MH+.)

Provenance & Evidence