Hydrochloric Acid → 1-(2-Methylsulfanyl-ethyl)-3,4-dihydro-isoquinoline-3-carboxylic acid methyl ester

반응식

C(Cl)(=O)C(Cl)=O.[CH3:7][O:8][C:9](=[O:25])[CH:10]([NH:18][C:19](=O)[CH2:20][CH2:21][S:22][CH3:23])[CH2:11][C:12]1[CH:17]=[CH:16][CH:15]=[CH:14][CH:13]=1.Cl>ClCCl>[CH3:7][O:8][C:9]([CH:10]1[CH2:11][C:12]2[C:17](=[CH:16][CH:15]=[CH:14][CH:13]=2)[C:19]([CH2:20][CH2:21][S:22][CH3:23])=[N:18]1)=[O:25]

참가 물질

실험 절차

0.882 mL (10.07 mmol) of oxalyl chloride was added dropwise to a solution of 2-(3-methylsulfanyl-propionylamino)-3-phenyl-propionic acid methyl ester (from previous step) in 30 mL of dichloromethane and stirred at room temperature for 1 h. This reaction mixture was then cooled to −10° C. and treated with 1.82 g (11 mmol) of FeCl3 at this temperature in portions. This reaction mixture was allowed to warm up to room temperature overnight. 30 mL of 2 N aq. HCl was added slowly while stirring for 1 h. 20 mL of dichloromethane was added and separated, washed again with water (50 mL), and dried over sodium sulfate. The organic solvents were evaporated in vacuo. The residual red solid was mixed with 30 mL of methanol and 1.5 mL of conc. H2SO4 and heated under reflux overnight. Water was added to the reaction mixture and the methanol was evaporated under reduced pressure. Ammonium hydroxide was added to adjust pH to basic. The aqueous layer (˜50 mL) was extracted with dichloromethane (2×50 mL). The combined organic layers were dried over sodium sulfate and evaporated. Purification by column chromatography on silica gel gave 923 mg (38%) of 1-(2-methylsulfanyl-ethyl)-3,4-dihydro-isoquinoline-3-carboxylic acid methyl ester. LCMS: 264 (M+1)+.