反应详情

A solution of 3-methyl-5,10-dihydropyrrolo[1,2-b]-isoquinoline-1,2-dicarboxylic acid dimethyl ester (2.39 g, 8 mmol) in anhydrous dichloromethane (20 mL) was added dropwise into a stirred suspension of LiAlH4 (0.69 g, 18.4 mmol) in anhydrous diethyl ether (30 mL) at 10-15° C. The reaction mixture was further stirred for 2 hours after the addition was completed. The mixture was cooled in an ice bath and the excess hydride was destroyed by the sequential addition of water (1.2 mL), 15% aqueous NaOH (1.2 mL), and water (3.6 mL) at 0° C. The mixture was filtered, and the inorganic solid was removed by filtration, washed with hot THF (300 mL). The combined filtrate and washings was evaporated in vacuo to dryness. The solid residue was recrystallized from dichloromethane/ether to give (2-hydroxymethyl-3-methyl-5,10-dihydropyrrolo[1,2-b]isoquinolin-1-yl)methanol (DA-1107), 1.47 g (76.2%); mp 99-101° C.; 1H NMR (DMSO-d6) δ 2.22 (3H, s, Me), 3.96 (2H, s, CH2), 4.34 and 4.39 (each 3H, brs, CH2 and exchangeable, OH), 4.93 (2H, s, CH2), 7.26 and 7.34 (each 2H, brs, 4×ArH); m/z 243.0 (M+H)+ Anal. Calcld. for C15H17NO2.0.1H2O): C, 73.50; H, 7.07; N, 5.71. Found: C, 73.42; H, 6.97; N, 5.71.

1. additionafter the addition
2. temperatureThe mixture was cooled in an ice bath
3. customthe excess hydride was destroyed by the sequential addition of water (1.2 mL), 15% aqueous NaOH (1.2 mL), and water (3.6 mL) at 0° C
4. filtrationThe mixture was filtered
5. customthe inorganic solid was removed by filtration
6. washwashed with hot THF (300 mL)
7. customThe combined filtrate and washings was evaporated in vacuo to dryness
8. customThe solid residue was recrystallized from dichloromethane/ether