Tert-butyl octahydropyrrolo(3,4-c)pyrrole-2-carboxylate → 2-(7-Boc-3,7-diazabicyclo[3.3.0]oct-3-yl)-xanthen-9-one

Participants

Reaction Conditions

Reaction Steps

A mixture of 3-Boc-3,7-diazabicyclo[3.3.0]octane (235 mg, 1.11 mmol; see WO 0181347), 2-iodoxanthen-9-one (362 mg, 1.12 mmol; see Example 52A), tris(dibenzylideneacetone)dipalladium (0) (Pd2(dba)3; 22 mg, 0.024 mmol; Alfa), racemic-2,2′-bis(diphenylphosphino)-1,1′-binaphthyl (BINAP; 37 mg, 0.059 mmol; Strem) and sodium tert-butoxide (166 mg, 1.73 mmol; Acros) in toluene (5 mL) was flushed with nitrogen and warmed to 85° C. with vigorous stirring for 6 h. The reaction mixture was cooled to ambient temperature, filtered through diatomaceous earth with an EtOAc rinse, concentrated under reduced pressure, and purified by flash chromatography (35 g silica gel, 5-50% gradient of EtOAc in hexanes) to afford the title compound as a yellow foam (275 mg, 0.677 mmol; 61% yield): 1H NMR (300 MHz, CDCl3) δ ppm 8.35 (dd, J=8, 2 Hz, 1H), 7.69 (ddd, J=9, 7, 2 Hz, 1H), 7.47 (d, J=8 Hz, 1H), 7.43 (d, J=9 Hz, 1H), 7.30-7.38 (m, 2H), 7.05 (dd, J=9, 3 Hz, 1H), 3.57-3.73 (m, 4H), 3.24-3.45 (m, 4H), 2.97-3.12 (m, 2H), 1.46 (s, 9H); MS (DCI/NH3): m/z 407 (M+1)+.

Provenance & Evidence