反应详情

In a sealed tube, add tris(dibenzylideneacetone)dipalladium (13 mg, 0.014 mmol) and 2,2′-bis(diphenylphosphino)-1,1′-binaphthyl (19 mg, 0.029 mmol) to a mixture of 6-(4-bromo-3-fluorobenzylthio)-3-tert-butoxycarbonyl-7-chloro-2,3,4,5-tetrahydro-1H-benzo[d]azepine (957 mg, 1.91 mmol), sodium tert-butoxide (367 mg, 3.83 mmol), 18-crown-6 (50 mg, 0.191 mmol) and piperidine (944 μl, 9.57 mmol) in toluene (10 mL). Flush the mixture with nitrogen and heat overnight. Cool to ambient temperature, dilute with water and extract three times with EtOAc. Dry over anhydrous Na2SO4 and concentrate in vacuo. Purify by chromatography on silica gel eluting with hexane/EtOAc (9:1) to give 3-tert-butoxycarbonyl-7-chloro-6-(3-fluoro-4-piperidin-1-yl-benzylthio)-2,3,4,5-tetrahydro-1H-benzo[d]azepine as a yellow oil (511 mg, 33%). Use a method similar to the General Procedure 1-4 to give the title compound as a white solid. MS (ES+) m/z: 405 (M+H)+.

1. customFlush the mixture with nitrogen
2. temperatureheat overnight
3. additiondilute with water
4. extractionextract three times with EtOAc
5. dry with materialDry over anhydrous Na2SO4
6. concentrationconcentrate in vacuo
7. customPurify by chromatography on silica gel eluting with hexane/EtOAc (9:1)