Potassium Carbonate → 2-[3-(5-Bromo-pyridin-2-yl)-propyl]-isoindole-1,3-dione

To a stirred solution of 2-allyl-isoindole-1,3-dione (3-1) (18.9 g, 101 mmol) in degassed TBF (100 mL) at 0° C. was added dropwise a solution of 9-BBN (243 mL of 0.5M in THF, 121 mmol) and the mixture stirred for 18 hours at ambient temperature. K2CO3 (24 g, 172 mmol) and 2,5-dibromopyridine (30 g, 126 mmol) were added, followed by a premixed and aged (70° C. for 30 min) suspension of Pd(OAc)2 (2.6 g, 11.5 mmol) and DPPF (7 g, 12.6 mmol) in degassed DMF (100 mL). The resulting mixture was stirred for 18 hours at 70° C., cooled, diluted with ethyl acetate, washed with water and brine, dried over MgSO4, and concentrated. To the stirring residue dissolved in TUF (500 mL) were added water (150 mL) and NaHCO3 (33 g) and after 10 minutes, NaBO3•H2O (55 g). After vigorous stirring for 30 minutes, the mixture was diluted with ethyl acetate, washed with water and brine, dried over MgSO4, and concentrated to an oil. The residue was chromatographed on silica gel (10-20% EtOAc/hexane) to give 13 g of 3-2 as a colorless oil.

1. additiona premixed
2. stirringThe resulting mixture was stirred for 18 hours at 70° C.
3. temperaturecooled
4. washwashed with water and brine
5. dry with materialdried over MgSO4
6. concentrationconcentrated
7. dissolutionTo the stirring residue dissolved in TUF (500 mL)
8. additionwere added water (150 mL) and NaHCO3 (33 g)
9. waitafter 10 minutes
10. stirringAfter vigorous stirring for 30 minutes
11. additionthe mixture was diluted with ethyl acetate
12. washwashed with water and brine
13. dry with materialdried over MgSO4
14. concentrationconcentrated to an oil
15. customThe residue was chromatographed on silica gel (10-20% EtOAc/hexane)

ORD-Eintrag

ord-d63b5ea7295c47c4b392779471d1970b

Quelldatensatz

uspto-grants-2002_10

DOI

10.6084/m9.figshare.5104873.v1

Patentnummer

US06472403B2