Sodium Carbonate → 5-(4-Fluorophenyl)pyridin-2-amine

HRID 1691648Notes

Reaction equation

HRID 1691648 reaction equation
[NH2:1][C:2]1[CH:7]=[CH:6][C:5](Br)=[CH:4][N:3]=1.[F:9][C:10]1[CH:15]=[CH:14][C:13](B(O)O)=[CH:12][CH:11]=1.C([O-])([O-])=O.[Na+].[Na+]>C1(C)C=CC=CC=1.C(O)C.O.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>[NH2:1][C:2]1[CH:7]=[CH:6][C:5]([C:13]2[CH:14]=[CH:15][C:10]([F:9])=[CH:11][CH:12]=2)=[CH:4][N:3]=1

Participants

8

Reactant 3

HCID 10340Sodium CarbonateHCID 706222-Amino-5-bromopyridineHCID 2856454-Fluorophenylboronic acid

Product 1

HCID 225048025-(4-Fluorophenyl)pyridin-2-amineYield 61.3%

Reagents, catalysts & solvents 4

HCID 178418397HCID 178418397, compoundCatalystHCID 702EthanolSolventHCID 962WaterSolventHCID 1140TolueneSolvent

Procedure

To a mixture of 2-amino-5-bromopyridine 1 (1.80 g, 10.4 mmol) in 104 ml toluene and 24 ml ethanol (EtOH) was added 4-fluorophenyl boronic acid (1.75 g, 12.5 mmol) followed by 10 ml of 2.0 M aqueous Na2CO3. The reaction was degassed with nitrogen and Pd(PPh3)4 (0.60 g, 0.52 mmol) was added in one portion and the reaction was heated to reflux for 26 hours. The reaction was then cooled to ambient temperature and diluted with 50 ml water. The layers were separated and the aqueous layer was extracted with ethyl acetate (EtOAc) (2×100 mL). The organic layers were combined, washed with saturated aqueous NaHCO3, dried over MgSO4 and concentrated to a brown oil. Automated purification on a silica gel ISCO column (120 g column, 2.5% MeOH—CH2Cl2) gave 1.20 g (60%) of 2-amino-5-(4-fluorophenyl)pyridine as a yellow solid.

Workup

  1. additionwas added in one portion
  2. temperaturethe reaction was heated
  3. temperatureto reflux for 26 hours
  4. customThe layers were separated
  5. extractionthe aqueous layer was extracted with ethyl acetate (EtOAc) (2×100 mL)
  6. washwashed with saturated aqueous NaHCO3
  7. dry with materialdried over MgSO4
  8. concentrationconcentrated to a brown oil
  9. custompurification on a silica gel ISCO column (120 g column, 2.5% MeOH—CH2Cl2)

Sources & evidence

ORD record
ord-ea40f7e1d5ae4b628eef1bbadcbdcc45
Source dataset
uspto-grants-2012_04
Patent number
US08153804B2

Reaction notes

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