Propylphosphonic anhydride → HCID 73505388, compound

Participants

Reaction Steps

To a stirred solution of 5′-(3-(3,5-dichloro-4-fluorophenyl)-3-(trifluoromethyl)-3,4-dihydro-2H-pyrrol-5-yl)-3′H-spiro[azetidine-3,1′-isobenzofuran]hydrochloride (Preparation 9, 0.43 g, 0.87mmol) in THF (10 mL) was added TEA (1.20 mL, 8.67 mmol). Methane sulfonyl acetic acid (0.239 g, 1.74mmol) and T3P (2.74 mL, 4.34mmol) were added at room temperature. Resulting reaction mixture was stirred at room temperature for 16 hours. After complete conversion of starting material, reaction mixture was quenched with water (10 mL) and extracted with ethyl acetate (3×10 mL). Combined organic layer was washed with brine (30 mL), dried over sodium sulfate and concentrated to get brown semi solid (0.46 g, crude). Crude compound was purified by column chromatography using Combiflash (redisep column, 12 g). Desired compound was eluted in 60% ethyl acetate in n-hexane to get off white solid (0.23 g. Impure). About 0.23 g was re-purified by preparative TLC to afford white solid (0.18 g). Compound was triturated with chloroform and n-Hexane and washed with distilled n-Hexane to get white solid (0.13 g, 25.9%). 1H NMR (400 MHz, CDCl3) δ: 3.19 (s, 3H), 3.43 (d, J=17.44 Hz, 1H), 3.78 (d, J=17.44 Hz, 1H), 3.86 (s, 2H), 4.34-4.46 (m, 3H), 4.64-4.69 (m, 2H), 4.87 (d, J=16.96 Hz, 1H), 5.16 (s, 2H), 7.32 (d, J=5.88 Hz, 2H), 7.58 (d, J=7.92 Hz, 1H), 7.77 (s, 1H), 7.83 (d, J=7.96 Hz, 1H), LC-MS (m/z): 576.9 (M−H).

Provenance & Evidence