2,2'-Bipyridine → HCID 86762596, compound

Temperature

70 °C

In a 2 L round bottom flask were added copper(II) acetate (8.9 g, 49 mmol) and 2,2′-bipyridine (7.8 g, 49 mmol) in 1,2-dichloroethane (240 ml). This was heated to 70° C. Separately were suspended 6-chloro-1H-pyrrolo[3,2-c]pyridine (15 g, 98 mmol) and cyclopropylboronic acid (17 g, 200 mmol) in 1,2-dichloroethane (240 ml). To the first heated mixture was added sodium carbonate (21 g, 200 mmol), followed by the second mixture, and the resulting mixture turned from green to dark red color. The mixture was heated to 70° C. overnight. Next day, conversion was ˜50%, and another 0.25 equivalent of Cu(OAc)2 (4.5 g), 0.25 equivalent of BiPy (3.9 g), and 1.0 equivalent of cyclopropylboronic acid (8.5 g) were added. The mixture was continued to stir at 70° C. for 12 hr. After cooling to room temperature, 250 ml brine and 250 ml EtOAc were added. The layers were separated, and the aqueous layer was extracted twice with EtOAc (2×150 ml). Copper salt was filtered from organic layers, which were then dried over sodium sulfate, filtered, and concentrated to obtain the crude product as a thick black oil. Dissolved in MeOH, the crude product was loaded onto silica before silica column chromatography. Collected fractions were pooled and concentrated to give a thick yellow oil containing bi-pyridine. To this oil were added 100 ml EtOAc and 100 ml saturated aqueous CuSO4 solution. The layers were separated, and the aqueous layer was separated to remove blue copper salt. The filtrate was then extracted twice with EtOAc (2×50 ml). Combined organic layers were dried with sodium sulfate, filtered and concentrated to obtain the product 6-chloro-1-cyclopropyl-1H-pyrrolo[3,2-c]pyridine (7A, 11 g, 57%) as a light yellow solid.

1. temperatureThe mixture was heated to 70° C. overnight
2. temperatureAfter cooling to room temperature
3. customThe layers were separated
4. extractionthe aqueous layer was extracted twice with EtOAc (2×150 ml)
5. filtrationCopper salt was filtered from organic layers, which
6. dry with materialwere then dried over sodium sulfate
7. filtrationfiltered
8. concentrationconcentrated
9. customto obtain the crude product as a thick black oil
10. concentrationconcentrated
11. customto give a thick yellow oil
12. customThe layers were separated
13. customthe aqueous layer was separated
14. customto remove blue copper salt
15. extractionThe filtrate was then extracted twice with EtOAc (2×50 ml)
16. dry with materialCombined organic layers were dried with sodium sulfate
17. filtrationfiltered
18. concentrationconcentrated

ORD record

ord-8923bcbc77324a1cb862cd8d0def2474

Source dataset

uspto-grants-2014_08

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US08802695B2