Pyridine → 6-Methylpyridine-2-carboxylic acid (6-acetyl-3-methoxy-2-methylphenyl)-amide

HRID 579637Notes

Reaction equation

[CH3:1][C:2]1[N:7]=[C:6]([C:8]([OH:10])=O)[CH:5]=[CH:4][CH:3]=1.[C:11]([C:14]1[C:19]([NH2:20])=[C:18]([CH3:21])[C:17]([O:22][CH3:23])=[CH:16][CH:15]=1)(=[O:13])[CH3:12].N1C=CC=CC=1.O=P(Cl)(Cl)Cl.[OH-].[Na+]>C(Cl)Cl.O>[C:11]([C:14]1[C:19]([NH:20][C:8]([C:6]2[CH:5]=[CH:4][CH:3]=[C:2]([CH3:1])[N:7]=2)=[O:10])=[C:18]([CH3:21])[C:17]([O:22][CH3:23])=[CH:16][CH:15]=1)(=[O:13])[CH3:12]

Participants

Conditions

Temperature: -5 °C

Procedure

6-Methylpicolinic acid (1.12 g, 8.167 mmol) was dissolved in dry DCM (100 ml) and kept on an ice-bath. Then, 6-acetyl-3-methoxy-2-methylaniline (1.48 g, 8.17 mmol) and pyridine (6.6 mL, 0.082 mol) were added followed by drop wise addition of POCl3 (1.53 mL, 0.016 mol) over 15 minutes. The resulting solution was stirred at −5° C. for 1 h. Then, water (100 mL) was added carefully and after 5 min of stirring, NaOH (40%, 20 mL) was subsequently added drop wise followed by the separation of the organic layer. The water layer was extracted three times with CH2Cl2, and the combined organic layers were washed with brine, dried (MgSO4), filtered and evaporated. The residue was purified by column chromatography (Heptane/AcOEt, 3:1) to give the title compound (2.1 g, 86%): m/z=299 (M+H)+.

Workup

customkept on an ice-bath
stirringof stirring
customwise followed by the separation of the organic layer
extractionThe water layer was extracted three times with CH2Cl2
washthe combined organic layers were washed with brine
dry with materialdried (MgSO4)
filtrationfiltered
customevaporated
customThe residue was purified by column chromatography (Heptane/AcOEt, 3:1)

Sources & evidence

ORD record: ord-27c45eeb7fde4087ae06329ebf69dfb9
Source dataset: uspto-grants-2015_05
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US09040562B2

Reaction notes

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