Water → 6-Bromo-3-(4-fluorophenyl)-imidazo[1,2-a]pyridine

HRID 629262Notes

Reaction equation

HRID 629262 reaction equation
[Br:1][C:2]1[CH:3]=[CH:4][C:5]2[N:6]([C:8](I)=[CH:9][N:10]=2)[CH:7]=1.[F:12][C:13]1[CH:18]=[CH:17][C:16](B(O)O)=[CH:15][CH:14]=1.C(=O)([O-])[O-].[Na+].[Na+].O>COCCOC.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>[Br:1][C:2]1[CH:3]=[CH:4][C:5]2[N:6]([C:8]([C:16]3[CH:17]=[CH:18][C:13]([F:12])=[CH:14][CH:15]=3)=[CH:9][N:10]=2)[CH:7]=1

Participants

7

Reactant 4

HCID 962WaterHCID 10340Sodium CarbonateHCID 2856454-Fluorophenylboronic acidHCID 220316326-Bromo-3-iodoimidazo(1,2-a)pyridine

Product 1

HCID 901891376-Bromo-3-(4-fluorophenyl)-imidazo[1,2-a]pyridineYield 48%

Reagents, catalysts & solvents 2

HCID 178418397HCID 178418397, compoundCatalystHCID 80711,2-DimethoxyethaneSolvent

Procedure

To a mixture of commercially available 6-bromo-3-iodoimidazo[1,2-a]pyridine (0.7 g, 2.17 mmol) and commercially available 4-fluoro-phenylboronic acid (0.3 g, 2.17 mmol) in 1,2-dimethoxyethane (14 ml), 2M sodium carbonate solution (2.71 ml, 5.42 mmol) was added, and the reaction mixture was purged with argon for 5 min in an ultrasonic bath. Afterwards tetrakis(triphenylphosphine)palladium(0) (125 mg, 108 μmol) was added, and the stirred reaction mixture was heated under reflux conditions for 17 h. The reaction mixture was cooled to room temperature, poured into water (30 ml) and extracted with ethyl acetate (2×40 ml). The combined organic layers were washed with brine (30 ml), dried (MgSO4) and evaporated. The crude material (0.74 g) was further purified by flash chromatography on silica gel (dichloromethane/MeOH 98:2) and trituration (diethyl ether) to yield the title compound as a light yellow solid (0.3 g, 48%), MS (ISP) m/z=291.3 [(M+H)+], mp 102° C.

Workup

  1. additionwas added
  2. customthe reaction mixture was purged with argon for 5 min in an ultrasonic bath
  3. customthe stirred reaction mixture
  4. temperaturewas heated under reflux conditions for 17 h
  5. extractionextracted with ethyl acetate (2×40 ml)
  6. washThe combined organic layers were washed with brine (30 ml)
  7. dry with materialdried (MgSO4)
  8. customevaporated
  9. customThe crude material (0.74 g) was further purified by flash chromatography on silica gel (dichloromethane/MeOH 98:2) and trituration (diethyl ether)

Sources & evidence

ORD record
ord-9291e0b5f4c94a37a126c240e8fd7a8d
Source dataset
uspto-grants-2016_04
Patent number
US09315502B2

Reaction notes

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