3-(Bromomethyl)-5-methylisoxazole → Ammonium Hydroxide

Participants

Reaction Conditions

Reaction Steps

A flask is charged with 3-methyl-2-pyridin-3-yl-1H-indole hydrochloride (Example 1, 0.100 g, 0.408 mmol) in THF (2.5 mL) and cooled to 0° C. KHMDS (0.5 M in toluene, 1.8 mL, 0.898 mmol) is added and the mixture is stirred at room temperature for 30 min, followed by addition of 3-bromomethyl-5-methyl-isoxazole (0.144 g, 0.817 mmol). The reaction mixture is stirred for 0.5 h, then quenched with saturated ammonium chloride solution and extracted with ethyl acetate. The organic layer is dried over sodium sulfate and concentrated in vacuo. The residue is purified by reverse phase HPLC with Xbridge Shield RP18 column and a 0.1% aqueous NH4OH in acetonitrile gradient to afford 3-methyl-1-(5-methyl-isoxazol-3-ylmethyl)-2-pyridin-3-yl-1H-indole product as a colorless oil. The oil is dissolved in diethyl ether and few drops of concentrated HCl are added. The volatiles are removed in vacuo and the reside is lyophilized to afford the product as a yellow solid. 1H NMR (400 MHz, MeOD) δ ppm (HCl salt) 2.30 (s, 3H), 2.31 (s, 3H), 5.30 (s, 2H), 5.67 (s, 1H), 7.18 (t, J=8.0 Hz, 1H), 7.27 (ddd, J=7.6, 1.1 Hz, 1H), 7.45 (d, J=8.1 Hz, 1H), 7.56-7.69 (m, 2H), 7.99 (dt, J=8.0, 1.9, 1.8 Hz, 1H), 8.56-8.68 (m, 2H). HRMS (ESI) m/z 304.1440 [(M+H)+ Calcd for C19H18N3O, 304.1450].

Provenance & Evidence