Phosphorus oxychloride → 6-Isopropylpyridine-2-carboxylic acid (6-acetyl-3-methoxy-2-methyl-phenyl)amide

HRID 407571Notes

Reaction equation

O=P(Cl)(Cl)Cl.[CH:6]([C:9]1[N:14]=[C:13]([C:15]([OH:17])=O)[CH:12]=[CH:11][CH:10]=1)([CH3:8])[CH3:7].[C:18]([C:21]1[C:26]([NH2:27])=[C:25]([CH3:28])[C:24]([O:29][CH3:30])=[CH:23][CH:22]=1)(=[O:20])[CH3:19].C(=O)(O)[O-].[Na+]>N1C=CC=CC=1>[C:18]([C:21]1[C:26]([NH:27][C:15]([C:13]2[CH:12]=[CH:11][CH:10]=[C:9]([CH:6]([CH3:7])[CH3:8])[N:14]=2)=[O:17])=[C:25]([CH3:28])[C:24]([O:29][CH3:30])=[CH:23][CH:22]=1)(=[O:20])[CH3:19]

Participants

Conditions

Temperature: -10 °C

Procedure

POCl3 (0.88 mL, 9.53 mmol) was added at −25° C. drop wise over 5 min under nitrogen, to a stirred solution of 6-isopropylpyridine-2-carboxylic acid (106, 1.43 g, 8.66 mmol) and 6-acetyl-3-metoxy-2-methylaniline (1.55 g, 8.66 mmol) in dry pyridine (70 mL). The resulting solution was stirred at −10° C. for 2.5 h. Then, the reaction mixture was poured on ice, neutralized with aqueous sodium bicarbonate and extracted 3 times with AcOEt. The organic layers were combined, washed with brine, dried (Na2SO4) and evaporated. The residue was purified by column chromatography (hexanes/AcOEt, 3:1) to give 3.54 g (72%) of the title compound 107: m/z=327 (M+H)+.

Workup

additionThen, the reaction mixture was poured on ice
extractionextracted 3 times with AcOEt
washwashed with brine
dry with materialdried (Na2SO4)
customevaporated
customThe residue was purified by column chromatography (hexanes/AcOEt, 3:1)

Sources & evidence

ORD record: ord-778ceb020f8841efb2d5d24ee42a1173
Source dataset: uspto-grants-2014_06
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US08754106B2

Reaction notes

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