Potassium Carbonate → 4-(4-Amino-2-chlorophenoxy)picolinamide

HRID 1670296Notes

Reaction equation

HRID 1670296 reaction equation
[NH2:1][C:2]1[CH:7]=[CH:6][C:5]([OH:8])=[C:4]([Cl:9])[CH:3]=1.CC([O-])(C)C.[K+].Cl[C:17]1[CH:22]=[CH:21][N:20]=[C:19]([C:23]([NH2:25])=[O:24])[CH:18]=1.C([O-])([O-])=O.[K+].[K+]>CN(C=O)C.CCOC(C)=O.O>[NH2:1][C:2]1[CH:7]=[CH:6][C:5]([O:8][C:17]2[CH:22]=[CH:21][N:20]=[C:19]([C:23]([NH2:25])=[O:24])[CH:18]=2)=[C:4]([Cl:9])[CH:3]=1

Participants

8

Reactant 4

HCID 11430Potassium CarbonateHCID 775784-Amino-2-chlorophenolHCID 3035434-Chloropyridine-2-carboxamideHCID 23665647Potassium tert-butoxide

Product 1

HCID 435176714-(4-Amino-2-chlorophenoxy)picolinamideYield 40.5%

Reagents, catalysts & solvents 3

HCID 962WaterSolventHCID 6228DimethylformamideSolventHCID 8857Ethyl AcetateSolvent

Procedure

To a solution of 4-amino-2-chlorophenol (Aldrich, 430 mg, 3.0 mmol) in DMF (2.0 mL) at room temperature was added KOt-Bu (352 mg, 3.2 mmol). The mixture was allowed to stir at room temperature for 1 h. To the solution were then added 4-chloropicolinamide (468 mg, 3.0 mmol) and K2CO3 (221 mg, 1.6 mmol). The resulting suspension was heated at 90° C. overnight. After cooling down, the suspension was diluted with 100 mL of EtOAc and 50 mL of H2O. The organic layer was separated and washed with brine (2×25 mL) and dried over MgSO4. After filtration and concentration, the solid was triturated with 50 mL of DCM. The solid was then collected and washed with DCM (2×20 mL), EtOAc (5.0 mL) and dried to give 4-(4-amino-2-chlorophenoxy)picolinamide (320 mg, 40% yield). MS (ESI+): m/z 264.12/266.07 (M+H)+.

Workup

  1. temperatureThe resulting suspension was heated at 90° C. overnight
  2. temperatureAfter cooling down
  3. customThe organic layer was separated
  4. washwashed with brine (2×25 mL)
  5. dry with materialdried over MgSO4
  6. filtrationAfter filtration and concentration
  7. customthe solid was triturated with 50 mL of DCM
  8. customThe solid was then collected
  9. washwashed with DCM (2×20 mL), EtOAc (5.0 mL)
  10. customdried

Sources & evidence

ORD record
ord-ca58851d263544f1974d9732aa611ffd
Source dataset
uspto-grants-2011_08
Patent number
US07989477B2

Reaction notes

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