Isopropanol → 1-[[2-Fluoro-6-(trifluoromethyl)phenyl]methyl]-6-methylpyrimidine-2,4-dione

HRID 1049104Notes

Reaction equation

HRID 1049104 reaction equation
[F:1][C:2]1[CH:12]=[CH:11][CH:10]=[C:9]([C:13]([F:16])([F:15])[F:14])[C:3]=1[CH2:4][NH:5][C:6]([NH2:8])=[O:7].[C:17](OC(C)(C)C)(=[O:22])[CH2:18][C:19]([CH3:21])=O.O.C1(C)C=CC(S(O)(=O)=O)=CC=1.CC(O)C>C1(C)C=CC=CC=1>[F:1][C:2]1[CH:12]=[CH:11][CH:10]=[C:9]([C:13]([F:14])([F:15])[F:16])[C:3]=1[CH2:4][N:5]1[C:19]([CH3:21])=[CH:18][C:17](=[O:22])[NH:8][C:6]1=[O:7]

Participants

6

Reactant 4

HCID 3776IsopropanolHCID 15538Tert-butyl acetoacetateHCID 521998p-Toluenesulfonic acid monohydrateHCID 22037856N-(2-Fluoro-6-(trifluoromethyl)benzyl)urea

Product 1

HCID 220378661-[[2-Fluoro-6-(trifluoromethyl)phenyl]methyl]-6-methylpyrimidine-2,4-dioneYield 63%

Reagents, catalysts & solvents 1

HCID 1140TolueneSolvent2×

Procedure

(2-Fluoro-6-trifluoromethyl-benzyl)-urea (2.568 g, 10.9 mmol) in toluene (125 mL) was heated briefly to reflux under a Dean-Stark trap. T-butyl acetoacetate (5.0 g) was added and the mixture heated to reflux for 4 hrs. p-Toluenesulfonic acid monohydrate (2.82 g, 14.8 mmol) was added and the reflux was continued for one additional hour. Toluene was displaced with i-PrOH and the volume of the solution was reduced to approximately 30 mL. The solution was stirred overnight at room temp. The crystalline product was filtered and washed with a few mL of i-PrOH to provide 2.01 g (63% yield) of 1-(2-fluoro-6-trifluoromethyl-benzyl)-6-methyl-1H-pyrimidine-2,4-dione. LCMS (ESI) m/z 303.0 (MH+)

Workup

  1. temperatureto reflux under a Dean-Stark trap
  2. temperaturethe mixture heated
  3. temperatureto reflux for 4 hrs
  4. filtrationThe crystalline product was filtered
  5. washwashed with a few mL of i-PrOH

Sources & evidence

ORD record
ord-f4a74de275b34758928d94d920773ea6
Source dataset
uspto-grants-2016_07
Patent number
US09382214B2

Reaction notes

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