Methyl acetoacetate → 4(3H)-Pyrimidinone, 6-methyl-2-[2-(trifluoromethyl)phenyl]-

HRID 1725587

Reaction equation

HRID 1725587 reaction equation
[F:1][C:2]([F:13])([F:12])[C:3]1[CH:11]=[CH:10][CH:9]=[CH:8][C:4]=1[C:5]([NH2:7])=[NH:6].[O-]CC.[Na+].[C:18](OC)(=[O:23])[CH2:19][C:20]([CH3:22])=O>C(O)C>[CH3:22][C:20]1[N:7]=[C:5]([C:4]2[CH:8]=[CH:9][CH:10]=[CH:11][C:3]=2[C:2]([F:12])([F:13])[F:1])[NH:6][C:18](=[O:23])[CH:19]=1

Participants

5

Reactant 3

HCID 7757Methyl acetoacetateHCID 2723922Sodium ethoxideHCID 32665092-Trifluoromethylbenzamidine

Product 1

HCID 1358508354(3H)-Pyrimidinone, 6-methyl-2-[2-(trifluoromethyl)phenyl]-Yield 50.2%

Reagents, catalysts & solvents 1

HCID 702EthanolSolvent

Procedure

A mixture of 2-trifluoromethyl-benzamidine (2.13 g, 4 mmol) and sodium ethoxide (0.83 g, 12 mmol) in ethanol (20 mL) was treated with methyl acetoacetate (0.44 mL, 4 mmol) and heated at for 24 hours. The reaction was cooled, concentrated, diluted with water and acidified with 2 N hydrochloric acid. The resulting solution was extracted with ethyl acetate, dried over sodium sulfate and concentrated. Purification by flash chromatography [SiO2, methanol:dichloromethane (3:97)] provided the title compound (0.51 g, 50% yield) as a yellow solid; 1H-NMR (500 MHz, DMSO-d6) δ 12.7 (br s, 1H), 7.9 (m, 1H), 7.8 (m, 2H), 7.7 (m, 1H), 6.3 (s, 1H), 2.21 (s, 3H) ppm; MS (FIA) 255.0 (M+H); Rt (Method A) 2.578 minutes.

Workup

  1. temperatureheated at for 24 hours
  2. temperatureThe reaction was cooled
  3. concentrationconcentrated
  4. additiondiluted with water
  5. extractionThe resulting solution was extracted with ethyl acetate
  6. dry with materialdried over sodium sulfate
  7. concentrationconcentrated
  8. customPurification by flash chromatography [SiO2, methanol:dichloromethane (3:97)]

Sources & evidence

ORD record
ord-422a949d7bad46dfb75b1eb3416d335f
Source dataset
uspto-grants-2009_02
Patent number
US07491730B2

Linked notes

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