Ethyl 4,4,4-trifluoroacetoacetate → 2-cyclopentyl-6-(trifluoromethyl)-1H-pyrimidin-4-one

HRID 1508936Notes

Reaction equation

HRID 1508936 reaction equation
[CH:1]1([C:6](=[NH:8])[NH2:7])[CH2:5][CH2:4][CH2:3][CH2:2]1.[F:9][C:10]([F:20])([F:19])[C:11](=O)[CH2:12][C:13](OCC)=[O:14].C[O-].[Na+]>C(O)C>[CH:1]1([C:6]2[N:7]=[C:13]([OH:14])[CH:12]=[C:11]([C:10]([F:20])([F:19])[F:9])[N:8]=2)[CH2:5][CH2:4][CH2:3][CH2:2]1

Participants

5

Reactant 3

HCID 67793Ethyl 4,4,4-trifluoroacetoacetateHCID 4452694CyclopentanecarboximidamideHCID 10942334Sodium Methoxide

Product 1

HCID 1785161402-cyclopentyl-6-(trifluoromethyl)-1H-pyrimidin-4-oneYield 36%

Reagents, catalysts & solvents 1

HCID 702EthanolSolvent

Conditions

Temperature
85 °C

Procedure

To a solution of cyclopentanecarboximidamide (3.0 g, 27.1 mmol) in ethanol (100 mL) was added ethyl 4,4,4-trifluoro-3-oxobutanoate (5.0 g, 27.1 mmol) and sodium methoxide (1.76 g, 32.5 mmol). The mixture was stirred at 85° C. for 16 h. After this time, the mixture was concentrated, diluted with ethanol (10 mL), and the suspension was chilled to 0° C. HCl (2M, 50 mL) was added and the suspension was filtered and washed with water. The solid was dried under heat and vacuum to afford the title compound (2.24 g, 36%) as a white solid. MW=232.20. 1H NMR (DMSO-d6, 500 MHz) δ 12.96 (s, 1H), 6.67 (s, 1H), 3.03 (quin, J=8.2 Hz, 1H), 2.00-1.92 (m, 2H), 1.83-1.67 (m, 4H), 1.64-1.53 (m, 2H); APCI MS m/z 233 [M+H]+.

Workup

  1. concentrationAfter this time, the mixture was concentrated
  2. additiondiluted with ethanol (10 mL)
  3. temperaturethe suspension was chilled to 0° C
  4. additionHCl (2M, 50 mL) was added
  5. filtrationthe suspension was filtered
  6. washwashed with water
  7. customThe solid was dried
  8. temperatureunder heat

Sources & evidence

ORD record
ord-7c18efbbe44b4843a10f55b107f3c576
Source dataset
uspto-grants-2015_12
Patent number
US09221843B2

Reaction notes

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