3,5-Dibromopyridine → (3aR,6aS)-tert-butyl 5-(5-bromopyridin-3-yl)hexahydropyrrolo[3,4-c]pyrrole-2(1H)-carboxylate

Temperature

70 °C

The product from example 1C (541 mg, 2.55 mmol) and 3,5-dibromopyridine (724 mg, 3.06 mmol) were combined in a 100 mL flask with toluene (14 mL). The solution was stirred at room temperature as sodium t-butoxide (367 mg, 3.82 mmol) was added as a solid. In a test tube, racemic-2,2′-bis(diphenylphosphino-1,1′-binaphthyl) (31 mg, 0.05 mmol) and tris(dibenzylideneacetone)dipalladium (0) (22 mg, 0.024 mmol) were combined with toluene (2 mL) and the mixture was heated at 70° C. for 5 min, then cooled to room temperature. This mixture was rinsed into the 100 mL flask with toluene (2 mL), and the reaction flask was evacuated and purged with nitrogen (3 cycles). The mixture was heated at 80° C. for 20 h, then cooled to room temperature and loaded onto a column of silica gel (45 g) and eluted with hexanes-EtOAc (1:1) to provide the titled compound as an off-white solid (0.51 g, 54%). 1H NMR (300 MHz, CD3OD) δ ppm 1.45 (s, 9H), 3.00-3.14 (m, 2H), 3.20-3.28 (m, 2H), 3.26-3.31 (m, 2H), 3.50-3.59 (m, 2H), 3.59-3.71 (m, 2H), 7.14-7.19 (m, 1H), 7.79-7.90 (m, 2H).

1. additionwas added as a solid
2. temperaturecooled to room temperature
3. washThis mixture was rinsed into the 100 mL flask with toluene (2 mL)
4. customthe reaction flask was evacuated
5. custompurged with nitrogen (3 cycles)
6. temperatureThe mixture was heated at 80° C. for 20 h
7. temperaturecooled to room temperature
8. washeluted with hexanes-EtOAc (1:1)

ORD record

ord-9ad80728c8a04ed89daed63b698cf700

Source dataset

uspto-grants-2014_02

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US08648084B2