Sodium hydride → 4-(4-Amino-3-chlorophenoxy)picolinamide

HRID 872969Notes

Reaction equation

HRID 872969 reaction equation
[ClH:1].[NH2:2][C:3]1[CH:8]=[CH:7][C:6]([OH:9])=[C:5](Cl)[CH:4]=1.[H-].[Na+].Cl[C:14]1[CH:19]=[CH:18][N:17]=[C:16]([C:20]([NH2:22])=[O:21])[CH:15]=1>CS(C)=O.O>[NH2:2][C:3]1[CH:8]=[CH:7][C:6]([O:9][C:14]2[CH:19]=[CH:18][N:17]=[C:16]([C:20]([NH2:22])=[O:21])[CH:15]=2)=[CH:5][C:4]=1[Cl:1]

Participants

6

Reactant 3

HCID 24758Sodium hydrideHCID 3035434-Chloropyridine-2-carboxamideHCID 198076694-Amino-2-chlorophenol hydrochloride

Product 1

HCID 231535844-(4-Amino-3-chlorophenoxy)picolinamideYield 29.3%

Reagents, catalysts & solvents 2

HCID 679Dimethyl SulfoxideSolventHCID 962WaterSolvent

Procedure

To a mixture of 4-amino-2-chlorophenol hydrochloride (446 mg, 2.4 mmol) in DMSO (4 mL) was added NaH (280 mg, 7.0 mmol, 60% dispersed in mineral oil). The reaction was stirred at rt for 30 minutes, followed by the addition of 4-chloropicolinamide (345 mg, 2.2 mmol). The reaction was microwaved at 160° C. for 2 hours, then cooled to rt, and diluted with water (20 mL). The resulted mixture was extracted with ethyl acetate (20 mL×3) and the combined organic phases were washed with brine (20 mL), dried over anhydrous Na2SO4, and concentrated in vacuo. The residue was purified by a silica gel column chromatography (EtOAc/PE (v/v)=1/1) to give the title compound as an orange solid (170 mg, 29%).

Workup

  1. customThe reaction was microwaved at 160° C. for 2 hours
  2. temperaturecooled to rt
  3. extractionThe resulted mixture was extracted with ethyl acetate (20 mL×3)
  4. washthe combined organic phases were washed with brine (20 mL)
  5. dry with materialdried over anhydrous Na2SO4
  6. concentrationconcentrated in vacuo
  7. customThe residue was purified by a silica gel column chromatography (EtOAc/PE (v/v)=1/1)

Sources & evidence

ORD record
ord-dbca14a16dd645ac9b172a1095cfd7d6
Source dataset
uspto-grants-2015_03
Patent number
US08975282B2

Reaction notes

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