Isoamyl Nitrite → 1,5-Dibromo-2-chloro-3-fluorobenzene

Temperature

70 °C

A solution of 2,6-dibromo-3-chloro-4-fluoro-phenylamine (1a, 4.85 g, 16 mmol, 1 eq.) in DMF (20 mL) was added to a solution of isoamylnitrite (3.46 mL, 25.6 mmol, 1.6 eq.) in DMF (12 mL) at 70° C. The mixture was heated at 70° C. for 3 h before it was cooled to room temperature, quenched with 1 N NaOH aqueous solution (150 mL), and extracted with EtOAc (200 mL). The EtOAc extract was washed with brine (100 mL×2), dried over MgSO4, filtered and concentrated. The residue was purified by flash chromatography (heptane) to give desired product 2a as colorless oil (3.70 g, 80%).

1. temperaturewas cooled to room temperature
2. customquenched with 1 N NaOH aqueous solution (150 mL)
3. extractionextracted with EtOAc (200 mL)
4. extractionThe EtOAc extract
5. washwas washed with brine (100 mL×2)
6. dry with materialdried over MgSO4
7. filtrationfiltered
8. concentrationconcentrated
9. customThe residue was purified by flash chromatography (heptane)

ORD record

ord-1542332200754fccbfc72f4ce284cc5a

Source dataset

uspto-grants-2015_12

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US09221827B2