Phthalimide → (+/-)-2-(3,6,7,8-tetrahydro-2H-indeno[4,5-b]furan-2-ylmethyl)-1H-isoindole-1,3(2H)-dione

참여 물질

반응 단계

To a solution of (±)-3,6,7,8-tetrahydro-2H-indeno[4,5-b]furan-2-ylmethanol (0.500 g, 2.63 mmol) in tetrahydrofuran (25 mL) was added triphenylphoshine (1.03 g, 3.94 mmol), phthalimide (0.58 g, 3.94 mmol) followed by diethylazodicarboxylate (0.687 g, 3.94 mmol) and the reaction mixture was allowed to stir at room temperature for 12 h. The reaction was quenched by the addition of water (5 mL) and the solvent was removed in vacuo. Purification by flash column chromatography (silica, ethyl acetate:hexanes 1:3) provided 0.65 g of (±)-2-(3,6,7,8-tetrahydro-2H-indeno[4,5-b]furan-2-ylmethyl)-1H-isoindole-1,3(2H)-dione as a white solid (mp 131-135° C.). The solid was re-dissolved in methanol (10 mL) and hydrazine monohydrate (0.153 g, 3.06 mmol) was added to the reaction mixture. The reaction mixture was heated at reflux for 12 h, concentrated hydrogen chloride (12.1 M, 3 mL) was added and heating was continued for an additional 1 h. The reaction mixture was cooled to room temperature and diluted with water (150 mL) and aqueous sodium hydroxide (2.5 N, 10 mL). The reaction mixture was extracted with ethyl acetate (2×75 mL) and the combined organic layers were dried (magnesium sulfate) and the solvent was removed in vacuo. Purification by flash column chromatography (silica, 10% aqueous ammonium hydroxide/methanol:ethyl acetate 1:19) provided a colorless oil. The oil was re-dissolved in isopropanol (1 mL) and hydrogen chloride (1.0 N in diethyl ether, 5 mL) was added. The resulting precipitate was filtered, washed (diethyl ether), and dried to afford 0.42 g (71%) of (±)-1-(3,6,7,8-tetrahydro-2H-indeno[4,5-b]furan-2-yl)methanamine as a white solid, hydrochloride salt. mp>230° C. (dec); Anal. calcd. for C12H15NOHCl: C, 63.85; H, 7.14; N, 6.21. Found: C, 63.64; H, 7.25; N, 6.02.

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