Toluene → Benzyl(4aR,7aR)-2-(benzoylamino)-7a-(5-cyanothiophen-2-yl)-4a,5,7,7a-tetrahydropyrrolo[3,4-d][1,3]thiazine-6(4H)-carboxylate

온도

145 °C

Benzyl (4aR,7aR)-2-(benzoylamino)-7a-(5-bromothiophen-2-yl)-4a,5,7,7a-tetrahydropyrrolo[3,4-d][1,3]thiazine-6(4H)-carboxylate (3.88 g, 6.97 mmol), anhydrous potassium hexacyanoferrate (II) (2.57 g, 6.97 mmol) (prepared as cited in Schareina, T.; et al Synthesis, 2008, 20, 3351-3355), copper (I) iodide (398 mg, 2.09 mmol), 1-butylimidazole (2.8 mL, 20.9 mmol), and toluene (23 mL) are added to a 60 mL glass pressure tube fitted with a stirrer bar. A stream of nitrogen is passed over the mixture for a few minutes and the pressure tube is then sealed. The stirred mixture is heated at 145° C. for 18 hours. The resulting dark mixture is cooled to room temperature. The mixture is diluted with ethyl acetate (100 mL) and water (15 mL) and vacuum filtered through a pad of diatomaceous earth while rinsing with ethyl acetate (100 mL) and water (15 mL). The layers of the filtrate are separated and the organic layer is further washed with water (2×30 mL) and brine (30 mL). The organic phase is dried over sodium sulfate, filtered, and concentrated under reduced pressure. The residue is purified by silica gel flash chromatography eluting with a hexanes/ethyl acetate, gradient from 80:20 to 0:100, to give the title compound (2.59 g, 74%) as a white foam: ES/MS (m/z): 503.2 (M+H).

1. customfitted with a stirrer bar
2. waitA stream of nitrogen is passed over the mixture for a few minutes
3. customthe pressure tube is then sealed
4. temperatureThe resulting dark mixture is cooled to room temperature
5. filtrationfiltered through a pad of diatomaceous earth
6. washwhile rinsing with ethyl acetate (100 mL) and water (15 mL)
7. customThe layers of the filtrate are separated
8. washthe organic layer is further washed with water (2×30 mL) and brine (30 mL)
9. dry with materialThe organic phase is dried over sodium sulfate
10. filtrationfiltered
11. concentrationconcentrated under reduced pressure
12. customThe residue is purified by silica gel flash chromatography
13. washeluting with a hexanes/ethyl acetate, gradient from 80:20 to 0:100

ORD 기록

ord-b4764b344aac40128a11ce0aaf2b7c0f

출처 데이터셋

uspto-grants-2014_11

DOI

10.6084/m9.figshare.5104873.v1

특허 번호

US08889856B2