Diethyl (ethoxymethylene)malonate → Ethyl 2-(3,5-difluorophenyl)-1,6-dihydro-1-(2-methoxyethyl)-6-oxo-5-pyrimidinecarboxylate

HRID 1846399Notes

Reaction equation

HRID 1846399 reaction equation
Cl.[F:2][C:3]1[CH:4]=[C:5]([C:10](=[NH:16])[NH:11][CH2:12][CH2:13][O:14][CH3:15])[CH:6]=[C:7]([F:9])[CH:8]=1.C([O:19][CH:20]=[C:21]([C:27](OCC)=O)[C:22]([O:24][CH2:25][CH3:26])=[O:23])C.[O-]CC.[Na+]>C(O)C>[F:2][C:3]1[CH:4]=[C:5]([C:10]2[N:11]([CH2:12][CH2:13][O:14][CH3:15])[C:20](=[O:19])[C:21]([C:22]([O:24][CH2:25][CH3:26])=[O:23])=[CH:27][N:16]=2)[CH:6]=[C:7]([F:9])[CH:8]=1

Participants

5

Reactant 3

HCID 6871Diethyl (ethoxymethylene)malonateHCID 2723922Sodium ethoxideHCID 178495960HCID 178495960, compound2×

Product 1

HCID 67955325Ethyl 2-(3,5-difluorophenyl)-1,6-dihydro-1-(2-methoxyethyl)-6-oxo-5-pyrimidinecarboxylate

Reagents, catalysts & solvents 1

HCID 702EthanolSolvent

Procedure

To a stirred solution of 3,5-difluoro-N-(2-methoxyethyl)benzenecarboximidamide hydrochloride (1:1 (i.e. the product from Example 9, Step B) (24.3 mmol) in ethanol (25 mL) was added diethyl ethoxymethylenemalonate (5.25 g, 24.3 mmol) followed by sodium ethoxide (21% soln) (9.1 mL, 24.3 mmol). The reaction mixture was heated and stirred at reflux for 24 h. The reaction mixture was cooled to room temperature concentrated under reduced pressure. The residue was purified by column chromatography eluting with 50% ethyl acetate in hexanes to afford the title product as a white solid (6.1 g).

Workup

  1. temperatureThe reaction mixture was heated
  2. temperatureat reflux for 24 h
  3. concentrationconcentrated under reduced pressure
  4. customThe residue was purified by column chromatography
  5. washeluting with 50% ethyl acetate in hexanes

Sources & evidence

ORD record
ord-bdc544b1b3004ae99cebf35175c59a03
Source dataset
uspto-grants-2015_02
Patent number
US08952024B2

Reaction notes

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