Triethylamine → 2-(4-Bromo-2,6-difluorophenyl)-2-(4-ethyl-3-oxo-1-oxa-4,9-diazaspiro[5.5]undecan-9-yl)acetamide

Participants

Reaction Conditions

Reaction Steps

To a solution of 2-(4-bromo-2,6-difluorophenyl)-2-hydroxyacetamide (0.86 g, 3.2 mmol) and triethylamine (1.4 mL, 9.7 mmol) in anhydrous acetonitrile (5 mL) was added neat methanesulfonyl chloride (0.33 mL, 4.2 mmol). The reaction mixture was stirred vigorously at 40° C. for 3 h, at which point the reaction had progressed to completion. To this mesylate intermediate mixture was added more triethylamine (1.4 mL, 9.7 mmol) followed by 4-ethyl-1-oxa-4,9-diazaspiro[5.5]undecan-3-one hydrochloride (0.11 g, 0.48 mmol). The reaction mixture was heated at 90° C. for 3 h until the starting material was consumed. The reaction was diluted with water and was extracted with ether (3×35 mL). The combined ether phases were dried over sodium sulfate, filtered, and evaporated under reduced pressure. Purification of the residue by flash chromatography (65-100% of 10% methanol in dichloromethane:dichloromethane) afforded the title product (261 mg, 18% yield). MS(ES)+ m/e 446 [M+H]+; 1H NMR (400 MHz, CD2Cl2) δ ppm 1.12 (t, J=7.20 Hz, 3 H) 1.64-1.71 (m, 1 H) 1.73 (dd, J=4.17, 2.65 Hz, 1 H) 1.90-1.99 (m, 2 H) 2.19-2.27 (m, 1 H) 2.54-2.66 (m, 1 H) 2.67-2.73 (m, 1 H) 2.75-2.81 (m, 1 H) 3.15 (s, 2 H) 3.41 (q, J=6.91 Hz, 2 H) 3.98 (s, 2 H) 4.69 (s, 1 H) 5.68 (br. s., 1 H) 7.15-7.25 (m, 2 H) 7.36 (br. s., 1 H).

Provenance & Evidence