Sodium Carbonate → 2,4-Dibromo-3,5-difluoro-6-(2-fluoro-5-nitrophenyl)pyridine

HRID 586276Notes

Reaction equation

Br[C:2]1[C:7]([F:8])=[C:6]([Br:9])[C:5]([F:10])=[C:4]([Br:11])[N:3]=1.[F:12][C:13]1[CH:18]=[CH:17][C:16]([N+:19]([O-:21])=[O:20])=[CH:15][C:14]=1B1OC(C)(C)C(C)(C)O1.C(=O)([O-])[O-].[Na+].[Na+]>C1C=CC([P]([Pd]([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)[P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)=CC=1.O1CCCC1>[Br:11][C:4]1[C:5]([F:10])=[C:6]([Br:9])[C:7]([F:8])=[C:2]([C:14]2[CH:15]=[C:16]([N+:19]([O-:21])=[O:20])[CH:17]=[CH:18][C:13]=2[F:12])[N:3]=1

Participants

Conditions

Temperature: 55 °C

Procedure

To a degassed mixture of 2,4,6-tribromo-3,5-difluoropyridine (4.26 g, 12.1 mmol), 2-(2-fluoro-5-nitrophenyl)-4,4,5,5-tetramethyl-[1,3,2]dioxaborolane (2.80 g, 10.4 mmol), aqueous sodium carbonate (10 ml of a 2 M solution), and tetrahydrofuran (40 ml) was added tetrakis(triphenylphosphine)palladium(0) (0.67 g). The mixture was then stirred at 55° C. for 48 h under an atmosphere of nitrogen. The reaction mixture was then partitioned between water and ethyl acetate. The organic layer was separated and evaporated, and the residue chromatographed (silica gel, 20-40% CH2Cl2/isohexane) to afford 1.209 g of 2,4-dibromo-3,5-difluoro-6-(2-fluoro-5-nitrophenyl)pyridine as a solid: 1H NMR (400 MHz, CDCl3) δ 7.37 (1H, t, J 8.8 Hz), 8.38 (1H, m), 8.55 (1H, dd, J 2.9, 6.1 Hz).

Workup

customThe reaction mixture was then partitioned between water and ethyl acetate
customThe organic layer was separated
customevaporated
customthe residue chromatographed (silica gel, 20-40% CH2Cl2/isohexane)

Sources & evidence

ORD record: ord-ac049f1414a641969bb0882ba0a9be5c
Source dataset: uspto-grants-2005_08
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US06936608B2

Reaction notes

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