Sodium hydride → 3-tert-butoxycarbonyl-7-chloro-6-(4-methyl-thiazol-2-ylthiomethyl)-2,3,4,5-tetrahydro-1H-benzo[d]azepine

To a solution of 4-methylthiazole-2-thiol (0.32 g, 2.5 mmol) in anhydrous DMF (8.4 mL) add sodium hydride (0.10 g, 2.6 mmol, 60% dispersion in mineral oil) in portions at room temperature. 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, 2.2 mmol) in anhydrous DMF (5.6 mL). Heat the reaction mixture at 45° C. for 2 h under nitrogen atmosphere, cool to room temperature and stir overnight. Quench the reaction mixture with 10% aqueous NaHCO3 (14 mL) and extract the mixture three times with EtOAc. Dry the combined organic extracts over Na2SO4, filter and concentrate in vacuo. Purify the crude mixture by chromatography on silica gel (40 g) eluting with hexane/EtOAc (1:0 to 85:15 gradient over 30 min; 35 mL/min) to obtain 3-tert-butoxycarbonyl-7-chloro-6-(4-methyl-thiazol-2-ylthiomethyl)-2,3,4,5-tetrahydro-1H-benzo[d]azepine (0.753 g, 79%) as a white foam.

1. temperatureHeat the reaction mixture at 45° C. for 2 h under nitrogen atmosphere
2. temperaturecool to room temperature
3. stirringstir overnight
4. customQuench the reaction mixture with 10% aqueous NaHCO3 (14 mL)
5. extractionextract the mixture three times with EtOAc
6. dry with materialDry the combined organic extracts over Na2SO4
7. filtrationfilter
8. concentrationconcentrate in vacuo
9. customPurify the crude mixture by chromatography on silica gel (40 g)
10. washeluting with hexane/EtOAc (1:0 to 85:15 gradient over 30 min; 35 mL/min)

ORDレコード

ord-4708fd177ad0479aba07061b029b715f

出典データセット

uspto-grants-2011_08

DOI

10.6084/m9.figshare.5104873.v1

特許番号

US07994163B2