Acetonitrile → Methyl 4-amino-5-chloro-6-(4-chlorophenyl)-3-methoxy-picolinate

HRID 407239Notes

Reaction equation

HRID 407239 reaction equation
[NH2:1][C:2]1[C:7]([Cl:8])=[C:6](Br)[N:5]=[C:4]([C:10]([O:12][CH3:13])=[O:11])[C:3]=1[O:14][CH3:15].[Cl:16][C:17]1[CH:22]=[CH:21][C:20](B(O)O)=[CH:19][CH:18]=1.[F-].[K+].CC#N>CCOC(C)=O.Cl[Pd](Cl)([P](C1C=CC=CC=1)(C1C=CC=CC=1)C1C=CC=CC=1)[P](C1C=CC=CC=1)(C1C=CC=CC=1)C1C=CC=CC=1.O>[NH2:1][C:2]1[C:7]([Cl:8])=[C:6]([C:20]2[CH:21]=[CH:22][C:17]([Cl:16])=[CH:18][CH:19]=2)[N:5]=[C:4]([C:10]([O:12][CH3:13])=[O:11])[C:3]=1[O:14][CH3:15]

Participants

8

Reactant 4

HCID 6342AcetonitrileHCID 742994-Chlorophenylboronic acidHCID 522689Potassium FluorideHCID 21696662Methyl 4-amino-6-bromo-5-chloro-3-methoxypicolinate

Product 1

HCID 71150551Methyl 4-amino-5-chloro-6-(4-chlorophenyl)-3-methoxy-picolinateYield 47.9%

Reagents, catalysts & solvents 3

HCID 178418476HCID 178418476, compoundCatalystHCID 962WaterSolventHCID 8857Ethyl AcetateSolvent

Conditions

Temperature
115 °C

Procedure

To a 5 mL microwave vial were added methyl 4-amino-6-bromo-5-chloro-3-methoxypicolinate (200 mg, 0.677 mmol), 4-chlorophenylboronic acid (116 mg, 0.744 mmol), KF (102 mg, 1.760 mmol), and PdCl2(PPh3)2 (48 mg, 0.068 mmol). Subsequently, CH3CN (1.1 mL) and H2O (1.1 mL) were added, and the reaction vial was sealed and heated in a Biotage microwave at 115° C. for 20 min. The reaction mixture was cooled to room temperature and diluted with EtOAc (3 mL). The organic phase was separated, and the aqueous phase was washed with EtOAc (2×2 mL). The organic extracts were combined, dried over Na2SO4, filtered, and concentrated in vacuo. The crude product was using a Teledyne ISCO purification system with a gradient eluent system of EtOAc and hexanes to yield the title compound as a white solid (106 mg, 47%): mp 139-141° C.; 1H NMR (400 MHz, DMSO-d6) δ 7.60-7.54 (m, 2H), 7.54-7.47 (m, 2H), 6.68 (s, 2H), 3.84 (s, 3H), 3.77 (s, 3H); ESIMS m/z 326.00 ([M−H]−).

Workup

  1. customthe reaction
  2. customvial was sealed
  3. temperatureThe reaction mixture was cooled to room temperature
  4. customThe organic phase was separated
  5. washthe aqueous phase was washed with EtOAc (2×2 mL)
  6. dry with materialdried over Na2SO4
  7. filtrationfiltered
  8. concentrationconcentrated in vacuo
  9. customa Teledyne ISCO purification system with a gradient eluent system of EtOAc and hexanes

Sources & evidence

ORD record
ord-c45ff9523c8240b9937e2d37dfee60b2
Source dataset
uspto-grants-2014_06
Patent number
US08754229B2

Reaction notes

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