反应详情

A solution of 3-(1-ethoxycarbonylmethyl-6,7-dimethoxy-3,4-dihydro-1H-isoquinolin-2-yl)-propionic acid ethyl ester (Helv. Chim. Acta 1958, 41, 119; 17.1 g, 45.0 mmol) in cyclohexane (340 mL) was treated with sodium ethylate (9.67 g, 135 mmol) and heated in an oil bath, and the ethanol formed during the reaction was removed by distillation over 30 min, while more cyclohexane was added in order to keep the reaction volume constant. After cooling the reaction mixture was neutralized with acetic acid and concentrated. The residue was dissolved in dichloromethane/water 1:1 and brought to pH 10 with concentrated ammonium hydroxide solution. The organic layer was separated, dried (MgSO4), and evaporated. The residue was dissolved in methanol (270 mL) and ammonium acetate (42.3 g, 548 mmol) was added. After stirring at r.t. for 90 min, the reaction mixture was evaporated and the residue partitioned between dichloromethane and 1 M aq. sodium hydroxide solution. The organic layer was dried (MgSO4), evaporated, and chromatographed (SiO2, CH2Cl2/MeOH/NH4OH 97.5:2.5:0.25) to afford the title compound (9.90 g, 66%). Light yellow solid, MS (ISP) 333.2 (M+H)+.

1. temperatureheated in an oil bath
2. customwas removed by distillation over 30 min, while more cyclohexane
3. additionwas added in order
4. temperatureAfter cooling the reaction mixture
5. concentrationconcentrated
6. dissolutionThe residue was dissolved in dichloromethane/water 1:1
7. customThe organic layer was separated
8. dry with materialdried (MgSO4)
9. customevaporated
10. dissolutionThe residue was dissolved in methanol (270 mL)
11. customthe reaction mixture was evaporated
12. customthe residue partitioned between dichloromethane and 1 M aq. sodium hydroxide solution
13. dry with materialThe organic layer was dried (MgSO4)
14. customevaporated
15. customchromatographed (SiO2, CH2Cl2/MeOH/NH4OH 97.5:2.5:0.25)