Sodium Carbonate → 4-(2-Chloro-5-nitrophenyl)-3-fluoropyridine

HRID 1963717Notes

Reaction equation

HRID 1963717 reaction equation
Br[C:2]1[CH:7]=[C:6]([N+:8]([O-:10])=[O:9])[CH:5]=[CH:4][C:3]=1[Cl:11].B(O)(O)[C:13]1[CH:18]=[CH:17][N:16]=[CH:15][C:14]=1[F:19].C(=O)([O-])[O-].[Na+].[Na+]>[Pd](Cl)Cl.C1(P(C2C=CC=CC=2)[C-]2C=CC=C2)C=CC=CC=1.[C-]1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=C1.[Fe+2].COCCOC.O>[Cl:11][C:3]1[CH:4]=[CH:5][C:6]([N+:8]([O-:10])=[O:9])=[CH:7][C:2]=1[C:13]1[CH:18]=[CH:17][N:16]=[CH:15][C:14]=1[F:19]

Participants

6

Reactant 3

HCID 10340Sodium CarbonateHCID 27355492-Bromo-1-chloro-4-nitrobenzeneHCID 27793533-Fluoropyridine-4-boronic acid

Product 1

HCID 690048774-(2-Chloro-5-nitrophenyl)-3-fluoropyridine

Reagents, catalysts & solvents 2

HCID 178418228Bis(cyclopenta-1,4-dien-1-yl(diphenyl)phosphane);dichloropalladium;iron(2+)CatalystHCID 18180031Water 1,2-dimethoxyethaneSolvent

Conditions

Temperature
100 °C

Procedure

A mixture of DME:H2O (3:1) was degassed with N2 for one half hour. 2-bromo-1-chloro-4-nitrobenzene (1 eq) added and degassed for another 10 minutes. 1,1′-bis(diphenylphosphino)ferrocene palladium(II)chloride (0.05 eq), 3-fluoropyridin-4-yl-4-boronic acid (1 eq), and sodium carbonate (3 eq) were then added and stirred at 100° C. for 16 hours. Reaction then concentrated and partitioned between ethyl acetate and water. Organic layer washed with brine, dried over sodium sulfate and concentrated. Purification on silica gel, 10% ethyl acetate in hexanes to yield 4-(2-chloro-5-nitrophenyl)-3-fluoropyridine. HPLC=4.57 min; MS: MH+=253.

Workup

  1. customwas degassed with N2 for one half hour
  2. customdegassed for another 10 minutes
  3. customReaction
  4. concentrationthen concentrated
  5. custompartitioned between ethyl acetate and water
  6. washOrganic layer washed with brine
  7. dry with materialdried over sodium sulfate
  8. concentrationconcentrated
  9. customPurification on silica gel, 10% ethyl acetate in hexanes

Sources & evidence

ORD record
ord-6bf0ece2009f411aba80df546ea4f9a0
Source dataset
uspto-grants-2013_04
Patent number
US08415382B2

Reaction notes

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