1,2,3,4-Tetrahydroisoquinoline → N-[3-(1,2,3,4-Tetrahydroisoquinolin-2-yl)propyl]acetoacetamide

Reaction equation

Br[CH2:2][CH2:3][CH2:4][NH:5][C:6](=[O:11])[CH2:7][C:8]([CH3:10])=[O:9].[CH2:12]1[C:21]2[C:16](=[CH:17][CH:18]=[CH:19][CH:20]=2)[CH2:15][CH2:14][NH:13]1.C([O-])([O-])=O.[K+].[K+]>CC(C)=O>[CH2:12]1[C:21]2[C:16](=[CH:17][CH:18]=[CH:19][CH:20]=2)[CH2:15][CH2:14][N:13]1[CH2:2][CH2:3][CH2:4][NH:5][C:6](=[O:11])[CH2:7][C:8]([CH3:10])=[O:9]

Participants

Procedure

A suspension of N-(3-bromopropyl)acetoacetamide (4.50 g, 20.3 mmol, 1.00 equiv), 1,2,3,4-tetrahydroisoquinoline (3.30 mL, 26.3 mmol, 1.30 equiv), K2CO3 (3.64 g, 26.3 mmol, 1.30 equiv), and KI (330 mg, 1.99 mmol, 0.10 equiv) in acetone (60 mL) was stirred at reflux for 14 hours. The mixture was cooled to room temperature, filtered, and concentrated. The residue was purified by flash chromatography (SiO2, MeOH-EtOAc 0:1 to 1:9) to give 1.78 g (43%) of light yellow oil, which was characterized spectroscopically. N-(3-Bromopropyl)acetoacetamide (1.20 g) was also recovered.