Citric Acid → HCID 57643150, compound

HRID 1057062Notes

Reaction equation

HRID 1057062 reaction equation
[Cl:1][C:2]1[CH:7]=[C:6](I)[CH:5]=[C:4]([Cl:9])[N:3]=1.[N:10]1[CH:15]=[CH:14][CH:13]=[C:12](B2OC(C)(C)C(C)(C)O2)[CH:11]=1.C1(P(C2CCCCC2)C2CCCCC2)CCCCC1.C(#N)C.[O-]P([O-])([O-])=O.[K+].[K+].[K+].C(O)(=O)CC(CC(O)=O)(C(O)=O)O>[Cl-].[Na+].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]>[Cl:1][C:2]1[CH:7]=[C:6]([C:12]2[CH:11]=[N:10][CH:15]=[CH:14][CH:13]=2)[CH:5]=[C:4]([Cl:9])[N:3]=1

Participants

9

Reactant 6

HCID 311Citric AcidHCID 6342AcetonitrileHCID 62657Potassium Phosphate, TribasicHCID 75806TricyclohexylphosphineHCID 27346563-(4,4,5,5-Tetramethyl-1,3,2-dioxaborolan-2-yl)pyridineHCID 117373932,6-Dichloro-4-iodopyridine

Product 1

HCID 57643150HCID 57643150, compoundYield 92.1%

Reagents, catalysts & solvents 2

HCID 9811564Bis(dibenzylideneacetone)palladiumCatalystHCID 57417360Sodium chloride; waterSolvent

Procedure

2,6-dichloro-4-iodopyridine (500 mg, 1.77082 mmol), 3-pyridylboronic acid pinacol ester (487 mg, 1.3 equiv., 2.30207 mmol), PCy3 (112 mg, 0.22 equiv., 0.389581 mmol), and Pd2(dba)3 (84 mg, 0.050 equiv., 0.0885411 mmol) were mixed in acetonitrile (13 mL, 140 equiv., 247.915 mmol) and K3PO4 (1.27 M, 1.95 mL, 1.4 equiv., 2.47915 mmol), and the reaction was kept at 110° C. for 2 h. Brine and 10% citric acid was used to adjust the pH around 8. The mixture was extracted with EtOAc three times. After evaporation of the organic layers, the residue was purified via chromatography (0-70% EtOAc/Heptane) to yield 367 mg yellow powder 1H NMR (400 MHz, CDCl3) δ (delta) 8.86 (d, J=2.4 Hz, 1H), 8.74 (dd, J=4.8, 1.6 Hz, 1H), 7.92-7.86 (m, 1H), 7.47 (s, 2H), 7.45 (dd, J=7.9, 4.8 Hz, 1H). 13C NMR (101 MHz, CDCl3) δ (delta) 151.45, 151.24, 150.72, 148.02, 134.40, 131.63, 123.96, 120.75. LCMS: m/z 225 (M+H).

Workup

  1. extractionThe mixture was extracted with EtOAc three times
  2. customAfter evaporation of the organic layers
  3. customthe residue was purified via chromatography (0-70% EtOAc/Heptane)

Sources & evidence

ORD record
ord-12c39c2cc6cd4ea09680b2bbc05c31f5
Source dataset
uspto-grants-2016_07
Patent number
US09399636B2

Reaction notes

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