Methanol → 6-Phenylpyridin-3-amine

HRID 2249496Notes

Reaction equation

HRID 2249496 reaction equation
[NH2:1][C:2]1[CH:3]=[N:4][C:5](Br)=[CH:6][CH:7]=1.CO.[C:11]1(B(O)O)[CH:16]=[CH:15][CH:14]=[CH:13][CH:12]=1.C([O-])([O-])=O.[K+].[K+]>C1COCC1.O>[C:11]1([C:5]2[N:4]=[CH:3][C:2]([NH2:1])=[CH:7][CH:6]=2)[CH:16]=[CH:15][CH:14]=[CH:13][CH:12]=1

Participants

7

Reactant 4

HCID 887MethanolHCID 11430Potassium CarbonateHCID 66827Phenylboronic AcidHCID 6428116-Bromopyridin-3-amine

Product 1

HCID 27628776-Phenylpyridin-3-amineYield 86.3%

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 8028TetrahydrofuranSolvent

Conditions

Temperature
70 °C

Procedure

To a solution of 3-amino-6-bromopyridine (1.1 g, 6.4 mmol) in THF (7 mL)-MeOH (7 mL) at RT was added phenylboronic acid (1.60 g, 12.8 mmol), PXPd (69 mg, 0.13 mmol), followed by K2CO3 (3.54 g, 25.6 mmol). The reaction mixture was stirred at 70° C. in a preheated oil bath for 16 h. After cooling to RT, the reaction mixture was poured into water (10 mL), and the resultant mixture was extracted with EtOAc (3×40 mL). The combined organic layers were washed with saturated NaCl, dried (Na2SO4), filtered and concentrated. The resulting residue was purified by silica gel (40 g) column chromatography eluting with a gradient of EtOAc (30-100%) in hexane to give the title compound as an off-white solid (940 mg, 86%). LC/MS (method A): retention time=1.28 min, (M+H)+=171.

Workup

  1. temperatureAfter cooling to RT
  2. extractionthe resultant mixture was extracted with EtOAc (3×40 mL)
  3. washThe combined organic layers were washed with saturated NaCl
  4. dry with materialdried (Na2SO4)
  5. filtrationfiltered
  6. concentrationconcentrated
  7. customThe resulting residue was purified by silica gel (40 g) column chromatography
  8. washeluting with a gradient of EtOAc (30-100%) in hexane

Sources & evidence

ORD record
ord-bd6229bc02ba4f9c9e4e3b78d497e8a6
Source dataset
uspto-grants-2008_01
Patent number
US07314882B2

Reaction notes

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