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

HRID 1061809Notes

Reaction equation

[F:1][C:2]1[C:3](Br)=[N:4][C:5]([Br:10])=[C:6]([F:9])[C:7]=1[Br:8].[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:10][C:5]1[C:6]([F:9])=[C:7]([Br:8])[C:2]([F:1])=[C:3]([C:14]2[CH:15]=[C:16]([N+:19]([O-:21])=[O:20])[CH:17]=[CH:18][C:13]=2[F:12])[N:4]=1

Participants

Conditions

Temperature: 55 °C

Procedure

To a degassed mixture of 3,5-difluoro-2,4,6-tribromopyridine (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 on silica gel eluting with isohexane on a gradient of dichloromethane (20-40%) to afford 2,4-dibromo-3,5-difluoro-6-(2-fluoro-5-nitrophenyl)pyridine as a solid (1.21 g): δH (400 MHz, CDCl3) 7.37 (1H, t, J 9), 8.38 (1H, m), 8.55 (1H, dd, J 6 and 3).

Workup

customThe reaction mixture was then partitioned between water and ethyl acetate
customThe organic layer was separated
customevaporated
customthe residue chromatographed on silica gel eluting with isohexane on a gradient of dichloromethane (20-40%)

Sources & evidence

ORD record: ord-fab249d3a90c4c12a7a737ca2f27166a
Source dataset: uspto-grants-2005_11
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US06960598B2

Reaction notes

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