Potassium Phosphate, Tribasic → N-(4-nitropyridin-2-yl)cyclopropanecarboxamide

HRID 1512192Notes

Reaction equation

HRID 1512192 reaction equation
Cl[C:2]1[CH:7]=[C:6]([N+:8]([O-:10])=[O:9])[CH:5]=[CH:4][N:3]=1.[CH:11]1([C:14]([NH2:16])=[O:15])[CH2:13][CH2:12]1.P([O-])([O-])([O-])=O.[K+].[K+].[K+].C1(P(C2CCCCC2)C2C=CC=CC=2C2C=CC=CC=2N(C)C)CCCCC1>C(COC)OC.C(OCC)(=O)C.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]>[N+:8]([C:6]1[CH:5]=[CH:4][N:3]=[C:2]([NH:16][C:14]([CH:11]2[CH2:13][CH2:12]2)=[O:15])[CH:7]=1)([O-:10])=[O:9]

Participants

8

Reactant 4

HCID 62657Potassium Phosphate, TribasicHCID 80376Cyclopropanecarboxamide2×HCID 7351522-Chloro-4-nitropyridineHCID 27342172-(Dicyclohexylphosphino)-2'-(dimethylamino)biphenyl

Product 1

HCID 58902368N-(4-nitropyridin-2-yl)cyclopropanecarboxamide

Reagents, catalysts & solvents 3

HCID 9811564Bis(dibenzylideneacetone)palladiumCatalystHCID 80711,2-DimethoxyethaneSolventHCID 8857Ethyl AcetateSolvent

Conditions

Temperature
90 °C

Procedure

2-Chloro-4-nitro-pyridine (476 mg, 3 mmol), cyclopropanecarboxylic acid amide (306 mg, 3.6 mmol), and tripotassium phosphate (892 mg, 4.2 mmol) are mixed in dimethoxyethane under an argon atmosphere. (2′-Dicyclohexylphosphanyl-biphenyl-2-yl)-dimethyl-amine (118 mg, 0.3 mmol) and Pd2(dba)3 (275 mg, 0.3 mmol) are added and the mixture is stirred for 3 h at 90° C. Further 0.5 equivalent cyclopropanecarboxylic acid amide (128 mg, 1.5 mmol) is added and the mixture is stirred for 1 additional hour. After cooling at RT the reaction mixture is taken in ethyl acetate, washed with a solution of saturated sodium hydrogen carbonate and brine. The combined organic phases are dried (Na2SO4), concentrated under reduced pressure and the residue is purified by column chromatography (ethyl acetate/hexane) to afford the title compound as a brown solid. M-H−=206.1, HPLC tR: 4.62 min.

Workup

  1. stirringthe mixture is stirred for 1 additional hour
  2. temperatureAfter cooling at RT the reaction mixture
  3. washwashed with a solution of saturated sodium hydrogen carbonate and brine
  4. dry with materialThe combined organic phases are dried (Na2SO4)
  5. concentrationconcentrated under reduced pressure
  6. customthe residue is purified by column chromatography (ethyl acetate/hexane)

Sources & evidence

ORD record
ord-00dd812c3d3e4068b2ea8db59d40b040
Source dataset
uspto-grants-2012_07
Patent number
US08217045B2

Reaction notes

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