2,2,6-Trimethyl-4H-1,3-dioxin-4-one → 1-(2,6-Difluorobenzyl)-2,6-dimethyl-3-ethoxycarbonyl-4-pyridone

HRID 495520Notes

Reaction equation

HRID 495520 reaction equation
[CH2:1]([O:3][C:4](=[O:18])/[CH:5]=[C:6](\[NH:8][CH2:9][C:10]1[C:15]([F:16])=[CH:14][CH:13]=[CH:12][C:11]=1[F:17])/[CH3:7])[CH3:2].CC1(C)[O:25][C:24](=O)[CH:23]=[C:22]([CH3:27])O1>C1(C)C=CC=CC=1>[F:16][C:15]1[CH:14]=[CH:13][CH:12]=[C:11]([F:17])[C:10]=1[CH2:9][N:8]1[C:22]([CH3:27])=[CH:23][C:24](=[O:25])[C:5]([C:4]([O:3][CH2:1][CH3:2])=[O:18])=[C:6]1[CH3:7]

Participants

4

Reactant 2

HCID 793682,2,6-Trimethyl-4H-1,3-dioxin-4-one2×HCID 69615320Ethyl-3-(2,6-difluorobenzylamino)crotonate

Product 1

HCID 223272431-(2,6-Difluorobenzyl)-2,6-dimethyl-3-ethoxycarbonyl-4-pyridoneYield 43%

Reagents, catalysts & solvents 1

HCID 1140TolueneSolvent

Procedure

A mixture of ethyl-3-(2,6-difluorobenzylamino)crotonate (2.55 g, 10.0 mmol) and 2,2,6-trimethyl-1,3-dioxin-4-one (1.85 g, 13.0 mmol) in toluene (100 mL) was heated at reflux for 3 hours. The reaction progress was monitored by LC/MS. An additional aliquot of 2,2,6-trimethyl-1,3-dioxin-4-one (2.0 mL) was added and the reaction mixture was refluxed for another 2 hours. LC/MS indicated complete conversion to product. The mixture was cooled down and the solvent was removed in vacuo. The solid residue was triturated with diethyl ether to yield the product as a tan solid (1.37 g, 4.3 mmol, 43%). 1H NMR (CDCl3, 300 MHz): 7.40-7.30 (m, 1H), 7.00-6.91 (m, 2H), 6.30 (s, 1H), 5.20 (s, 2H), 4.37 (q, J=6.9 Hz, 2H), 2.37 (s, 3H), 2.31 (s, 3H), 1.35 (t, J=6.9 Hz, 3H); LRMS m/z 322.1 (M++1).

Workup

  1. temperaturewas heated
  2. temperatureat reflux for 3 hours
  3. temperaturethe reaction mixture was refluxed for another 2 hours
  4. temperatureThe mixture was cooled down
  5. customthe solvent was removed in vacuo
  6. customThe solid residue was triturated with diethyl ether

Sources & evidence

ORD record
ord-3c46818095a5485fb25c13e9973daaf4
Source dataset
uspto-grants-2005_09
Patent number
US06939883B2

Reaction notes

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