Butyl vinyl ether → tert-butyl 5'-acetyl-3'H-spiro[azetidine-3,1'-isobenzofuran]-1-carboxylate

Participants

Reaction Conditions

Reaction Steps

In 100 mL autoclave vessel a solution of tert-butyl 5′-bromo-3′H-spiro[azetidine-3,1′-isobenzofuran]-1-carboxylate (Intermediate 1, 10 g, 29.4 mmol) in ethanol (35 mL) was degassed with nitrogen gas for 30 minutes. To the resulting reaction mixture was added TEA (7.37 mL, 52.9 mmol), butyl vinyl ether (7.60 mL, 58.8 mmol), dppp (0.727 g, 1.8 mmol) followed by addition of Pd(OAc)2 (0.198 g, 0.9 mmol) at room temperature. Reaction mixture was heated at 96° C. for 16 hours in autoclave. After complete consumption of starting material, reaction mixture was quenched with addition of 1N HCl (10 mL) to adjust pH 2-3 then reaction mixture was stirred for 2 hours. The pH of reaction mixture was adjusted to 7 by addition of saturated NaHCO3 solution and extracted with ethyl acetate (3×100 mL). Combined organic layers were washed with brine (250 mL), dried over sodium sulfate and concentrated under reduced pressure to get crude compound as dark brown sticky oil 12 g as crude material. The crude was purified by column chromatography on silica gel using 230-400 silica mesh. Desired compound was eluted in 30% ethyl acetate in n-hexane to give (8.4 g) compound as off white sticky semi-solid. 1H NMR (400 MHz, CDCl3) δ: 1.47 (s, 9H), 2.61 (s, 3H), 4.13 (d, J=9.64 Hz, 2H), 4.32 (d, J=9.52 Hz, 2H), 5.14 (s, 2H), 7.54 (d, J=7.96 Hz, 1H), 7.80 (s, 1H), 7.97 (d, J=7.92 Hz, 1H); VETERINARY (m/z): 304.0 (M+H).

Provenance & Evidence