Toluene → 5-Phenylpyridin-3-amine

HRID 1875893Notes

Reaction equation

HRID 1875893 reaction equation
Br[C:2]1[CH:3]=[C:4]([NH2:8])[CH:5]=[N:6][CH:7]=1.[C:9]1(C)[CH:14]=[CH:13][CH:12]=[CH:11][CH:10]=1.C(=O)([O-])[O-].[Na+].[Na+].C1(B(O)O)C=CC=CC=1>C(O)C.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>[C:9]1([C:2]2[CH:3]=[C:4]([NH2:8])[CH:5]=[N:6][CH:7]=2)[CH:14]=[CH:13][CH:12]=[CH:11][CH:10]=1

Participants

7

Reactant 4

HCID 1140TolueneHCID 10340Sodium CarbonateHCID 66827Phenylboronic AcidHCID 8176813-Amino-5-bromopyridine

Product 1

HCID 27629015-Phenylpyridin-3-amineYield 13%

Reagents, catalysts & solvents 2

HCID 178418397HCID 178418397, compoundCatalystHCID 702EthanolSolvent

Conditions

Temperature
90 °C

Procedure

A mixture of 5-bromopyridin-3-amine (248 mg, 1.43 mmol), Pd(PPh3)4 (50.4 mg, 0.04 mmol), toluene (3 mL), sodium carbonate (2 M, 3 mL, 6 mmol), and phenylboronic acid (195 mg, 1.60 mmol) dissolved in ethanol (3 mL) was heated for 4 hours in an oil bath at 90° C. and allowed to cool to room temperature for 16 hours. The reaction mixture was transferred to a separatory funnel and partitioned between ethyl acetate and water. The aqueous phase was washed once more with ethyl acetate, and the combined organic phases were washed with brine and dried over magnesium sulfate, filtered and concentrated in vacuo. The residue was purified by column chromatography (80% ethyl acetate/hexanes) to afford 5-phenylpyridin-3-amine (31.9 mg, 0.19 mmol, 13% yield) as a white solid. 1H NMR (500 MHz, CDCl3) δ ppm 8.17-8.42 (m, 1H), 8.02-8.20 (m, 1H), 7.32-7.62 (m, 4H), 7.25 (s, 1H), 7.06-7.20 (m, 1H). MS (LC/MS) R.T.=0.91; [M+H]+=171.09.

Workup

  1. temperatureto cool to room temperature for 16 hours
  2. customThe reaction mixture was transferred to a separatory funnel
  3. custompartitioned between ethyl acetate and water
  4. washThe aqueous phase was washed once more with ethyl acetate
  5. washthe combined organic phases were washed with brine
  6. dry with materialdried over magnesium sulfate
  7. filtrationfiltered
  8. concentrationconcentrated in vacuo
  9. customThe residue was purified by column chromatography (80% ethyl acetate/hexanes)

Sources & evidence

ORD record
ord-eea279b5805744b099a3a3510fd22fe2
Source dataset
uspto-grants-2012_11
Patent number
US08309577B2

Reaction notes

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