1,4-Dibromobenzene → HCID 68705128, compound

Temperature

-78 °C

To a solution of 1,4-dibromobenzene (407.5 mg, 1.727 mmol) in THF (6 ml) was added n-BuLi (2.5 M in hexanes, 0.691 ml, 1.727 mmol) at −78° C. The mixture was stirred at the temperature for 30 minutes before the addition of a solution of the above amide (203.8 mg, 0.8636 mmol) in THF (4 ml). After stirring at −78° C. for 30 minutes, the mixture was warmed to room temperature for 1 hour. EtOAc (40 ml) and water (15 ml) was added to the reaction, followed by separation of the layers. The aqueous phase was extracted with EtOAc (15 ml). The combined organic layers were washed with brine (10 ml), dried (MgSO4), filtered, and concentrated under reduced pressure to furnish the crude product. This material was purified by column chromatography (40% acetone/hexanes) to furnish (4-bromo-phenyl)-(1-pyrimidin-2-yl-pyrrolidin-3-yl)-methanone (182.2 mg, 64%) as an off-white solid: 1H NMR (CDCl3, 400 MHz) δ 8.32 (d, J=6.4 Hz, 2H), 7.87 (d, J=12.0 Hz, 2H), 7.63 (d, J=12.0 Hz, 2H), 6.51 (t, J=6.4 Hz, 1H), 4.07 (m, 1H), 3.98 (m, 1H), 3.86 (m, 1H), 3.74 (m, 2H), 2.38 (m, 2H).

1. temperaturethe mixture was warmed to room temperature for 1 hour
2. customfollowed by separation of the layers
3. extractionThe aqueous phase was extracted with EtOAc (15 ml)
4. washThe combined organic layers were washed with brine (10 ml)
5. dry with materialdried (MgSO4)
6. filtrationfiltered
7. concentrationconcentrated under reduced pressure
8. customto furnish the crude product
9. customThis material was purified by column chromatography (40% acetone/hexanes)

ORD record

ord-a0c430317f154fa3b738d4580c7a038d

Source dataset

uspto-grants-2014_07

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US08772291B2