Potassium Phosphate, Tribasic → 5-Benzylpyridin-2-amine

HRID 2075269Notes

Reaction equation

HRID 2075269 reaction equation
[CH2:1](B1C2CCCC1CCC2)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.I[C:18]1[CH:19]=[CH:20][C:21]([NH2:24])=[N:22][CH:23]=1.P([O-])([O-])([O-])=O.[K+].[K+].[K+].CC(C1C=C(C(C)C)C(C2C=CC=CC=2P(C2CCCCC2)C2CCCCC2)=C(C(C)C)C=1)C>O.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.[Pd].[Pd]>[CH2:1]([C:18]1[CH:19]=[CH:20][C:21]([NH2:24])=[N:22][CH:23]=1)[C:2]1[CH:3]=[CH:4][CH:5]=[CH:6][CH:7]=1

Participants

7

Reactant 4

HCID 62657Potassium Phosphate, TribasicHCID 885792-Pyridinamine, 5-iodo-HCID 41509249-Benzyl-9-borabicyclo(3.3.1)nonaneHCID 111557942-Dicyclohexylphosphino-2',4',6'-triisoprophylbiphenyl

Product 1

HCID 134300735-Benzylpyridin-2-amine

Reagents, catalysts & solvents 2

HCID 9811564Bis(dibenzylideneacetone)palladiumCatalystHCID 962WaterSolvent

Conditions

Temperature
120 °C

Procedure

9-Benzyl-9-bora-bicyclo[3.3.1]nonane (0.5M solution in THF, 12727 μL, 6363 μmol) was added to a mixture of 5-iodopyridin-2-amine (700 mg, 3182 μmol), potassium phosphate (2026 mg, 9545 μmol), Pd2 dba3 (58 mg, 64 μmol), and X-Phos (61 mg, 127 μmol) suspended in H2O (1 mL) in a sealable reaction vial. The vial was flushed with argon gas and then sealed and heated (microwave) at 120° C. for 30 min. The crude mixture was diluted with EtOAc, and the resulting solution was sequentially washed with 1M NaOH and brine. The organic layer was dried over sodium sulfate and concentrated in vacuo. The residue was taken up in MeOH (5 mL), concentrated aqueous HCl (0.30 mL) was added, and the resulting solution was stirred 10 min. Solid NaOH (120 mg) was then added, and the resulting solution was concentrated onto silica gel. Chromatographic purification of the product (ISCO, 12 g, 0-10% MeOH/CH2Cl2) furnished 5-benzylpyridin-2-amine as a yellow solid. 1H NMR (400 MHz, CHLOROFORM-d) δ ppm 7.95 (s, 1H), 7.28 (t, J=7.5 Hz, 2H), 7.23 (d, J=11.0 Hz, 2H), 7.17 (t, J=8.5 Hz, 2H), 6.44 (d, J=8.5 Hz, 1H), 4.34 (s, 2H), 3.80-3.86 (m, 2H).

Workup

  1. customThe vial was flushed with argon gas
  2. customsealed
  3. additionThe crude mixture was diluted with EtOAc
  4. washthe resulting solution was sequentially washed with 1M NaOH and brine
  5. dry with materialThe organic layer was dried over sodium sulfate
  6. concentrationconcentrated in vacuo
  7. additionconcentrated aqueous HCl (0.30 mL) was added
  8. additionSolid NaOH (120 mg) was then added
  9. concentrationthe resulting solution was concentrated onto silica gel
  10. customChromatographic purification of the product (ISCO, 12 g, 0-10% MeOH/CH2Cl2)

Sources & evidence

ORD record
ord-e80af44b8616444489db23086ab2d17c
Source dataset
uspto-grants-2011_04
Patent number
US07919519B2

Reaction notes

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