反应详情

A solution of 1-benzhydryl-3-isopropylaminoazetidine-3-carbonitrile (I-3A-1a; 3.40 g, 11.1 mmol) in methylene chloride (25 ml) cooled in an ice bath was treated with H2SO4 (5.95 ml, 111 mmol), dropwise. After the reaction mixture was allowed to warm to room temperature and stir overnight, it was cooled in an ice bath and then carefully quenched with concentrated NH4OH to pH 11. The mixture was extracted with methylene chloride, the combined organic layers were dried (Na2SO4) and then concentrated, in vacuo, to afford a crude foam (3.3 g) that was then purified on a Biotage™ Flash 40M column using 0-2% methanol in methylene chloride as eluant to afford the title compound I-3A-1b (2.32 g, 64%) as a brown solid: +ESI MS (M+1) 324.4; 1H NMR (400 MHz, CD3OD) δ 7.40 (d, J=7.5 Hz, 4H), 7.24 (t, J=7.5 Hz, 4H), 7.15 (t, J=7.1 Hz, 2H), 4.46 (s, 1H), 3.53 (d, J=8.7 Hz, 2H), 3.06 (d, J=8.7 Hz, 2H), 2.90 (septuplet, J=6.4 Hz, 1H), 0.97 (d, J=6.6 Hz, 6H).

1. temperatureit was cooled in an ice bath
2. customcarefully quenched with concentrated NH4OH to pH 11
3. extractionThe mixture was extracted with methylene chloride
4. dry with materialthe combined organic layers were dried (Na2SO4)
5. concentrationconcentrated, in vacuo
6. customto afford a crude foam (3.3 g) that
7. customwas then purified on a Biotage™ Flash 40M column