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

HRID 451442Notes

Reaction equation

HRID 451442 reaction equation
Br[C:2]1[CH:3]=[CH:4][C:5]([NH2:8])=[N:6][CH:7]=1.[CH:9]1(B(O)O)[CH2:11][CH2:10]1.[O-]P([O-])([O-])=O.[K+].[K+].[K+]>C1(C)C=CC=CC=1.O.CC([O-])=O.CC([O-])=O.[Pd+2]>[CH:9]1([C:2]2[CH:3]=[CH:4][C:5]([NH2:8])=[N:6][CH:7]=2)[CH2:11][CH2:10]1

Participants

7

Reactant 3

HCID 62657Potassium Phosphate, TribasicHCID 706222-Amino-5-bromopyridineHCID 2760897Cyclopropylboronic acid

Product 1

HCID 230048695-Cyclopropylpyridin-2-amine

Reagents, catalysts & solvents 3

HCID 167845palladium(II) acetateCatalystHCID 962WaterSolvent2×HCID 1140TolueneSolvent

Conditions

Temperature
80 °C

Procedure

To a solution of 5-bromo-pyridin-2-ylamine (2 g, 11.55 mmol) and cyclopropyl boronic acid (2.98 g, 34.68 mmol) in toluene (40 mL) and water (2 mL) was added K3PO4 (8.59 g, 40.46 mmol) under an argon atmosphere. To this were added Pd(OAc)2 (259.52 mg, 1.16 mmol) and tricyclohexylphosphene (647.3 mg, 2.3 mmol) and stirred at 80° C. for 16 hours. The reaction mixture was cooled to room temperature and water was added. The aqueous phase was extracted with ethyl acetate, the combined organic phases were dried over sodium sulfate, the solvent was evaporated and the residue purified by silica gel chromatography using ethyl acetate/hexane as eluent. The title compound was obtained as an off white solid (1.1 g, 71%).

Workup

  1. temperatureThe reaction mixture was cooled to room temperature
  2. extractionThe aqueous phase was extracted with ethyl acetate
  3. dry with materialthe combined organic phases were dried over sodium sulfate
  4. customthe solvent was evaporated
  5. customthe residue purified by silica gel chromatography

Sources & evidence

ORD record
ord-ed57d874183d410cbac3c01e1f17fd78
Source dataset
uspto-grants-2013_07
Patent number
US08486967B2

Reaction notes

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