2-Butenoic acid, 3-amino-, ethyl ester, (2Z)- → ethyl 6-hydroxy-2-methyl-4-oxo-1H-pyridine-3-carboxylate

HRID 1498623Notes

Reaction equation

ClC1C=C(Cl)C=C(Cl)C=1[O:10][C:11](=O)[CH2:12][C:13](OC1C(Cl)=CC(Cl)=CC=1Cl)=[O:14].[NH2:26]/[C:27](/[CH3:34])=[CH:28]\[C:29]([O:31][CH2:32][CH3:33])=[O:30]>BrC1C=CC=CC=1.CCOC(C)=O>[CH2:32]([O:31][C:29](=[O:30])[C:28]1[C:11]([OH:10])=[CH:12][C:13]([OH:14])=[N:26][C:27]=1[CH3:34])[CH3:33]

Participants

Conditions

Temperature: 50 °C

Procedure

A mixture of malonic acid (20 g, 192 mmol), 2,4,6-trichlorophenol (72 g, 365 mmol), and phosphorus oxychloride (38 mL, 403.2 mmol) was stirred at reflux for 12 h. The reaction mixture was cooled to 70° C. and poured into ice water. The solid was collected by filtration, washed with water, and air-dried to give malonic acid bis-(2,4,6-trichloro-phenyl) ester (85 g, 95%). A solution of malonic acid bis-(2,4,6-trichloro-phenyl) ester (85 g, 183.6 mmol) and ethyl 3-aminocrotonate (26.1 g, 202 mmol) in bromobenzene (100 mL) was stirred at reflux for 50 min. The reaction mixture was cooled to 50° C. and diluted with EtOAc (260 mL). The solid was collected by filtration, washed with water, and air-dried, to give 4,6-dihydroxy-2-methyl nicotinic acid ethyl ester (31 g, 86%).

Workup

temperatureat reflux for 50 min
filtrationThe solid was collected by filtration
washwashed with water
customair-dried

Sources & evidence

ORD record: ord-b50fe7193e8a4f2ebd2478027ac11b36
Source dataset: uspto-grants-2015_12
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US09199990B2

Reaction notes

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