反应详情

To a solution of 2-mercaptothiazoline (0.3 g, 2.5 mmol) in anhydrous DMF (8.5 mL) at room temperature add sodium hydride (0.1 g, 2.6 mmol, 60% dispersion in mineral oil) in portions. After stirring at room temperature for 10 min, add a solution of 3-tert-butoxycarbonyl-7-chloro-6-chloromethyl-2,3,4,5-tetrahydro-1H-benzo[d]azepine (0.74 g, 2.3 mmol) in anhydrous DMF (5.6 mL). Stir at room temperature overnight and quench the reaction mixture with 10% aqueous NaHCO3 (14 mL). Extract the mixture twice with EtOAc. Dry the combined organic extracts over Na2SO4, filter and concentrate in vacuo. Dissolve the residue in DCM, load the solution on to a RediSep® column (40 g) and purify the crude mixture by preparative liquid chromatography (100:0 to 95:5 hexane/EtOAc over 30 min; 95:5 hexane/EtOAc over 3 min; 95:5 to 75:25 hexane/EtOAc over 30 min; 75:25 hexane/EtOAc over 3 min; 35 mL/min) to afford 3-tert-butoxycarbonyl-7-chloro-6-(4,5-dihydro-thiazol-2-ylthiomethyl)-2,3,4,5-tetrahydro-1H-benzo[d]azepine (0.77 g, 83%). MS (ES+) m/z: 413.1 (M+H)+.

1. stirringStir at room temperature overnight
2. customquench the reaction mixture with 10% aqueous NaHCO3 (14 mL)
3. extractionExtract the mixture twice with EtOAc
4. dry with materialDry the combined organic extracts over Na2SO4
5. filtrationfilter
6. concentrationconcentrate in vacuo
7. dissolutionDissolve the residue in DCM
8. customload the solution on to a RediSep® column (40 g) and purify the crude mixture by preparative liquid chromatography (100:0 to 95:5 hexane/EtOAc over 30 min; 95:5 hexane/EtOAc over 3 min; 95:5 to 75:25 hexane/EtOAc over 30 min; 75:25 hexane/EtOAc over 3 min; 35 mL/min)