Acetic Acid → Ethyl 4-(2-fluorophenyl)-6-methyl-2-oxo-1,2,3,4-tetrahydropyrimidine-5-carboxylate

HRID 1036619Notes

Reaction equation

HRID 1036619 reaction equation
[F:1][C:2]1[CH:9]=[CH:8][CH:7]=[CH:6][C:3]=1[CH:4]=O.[NH2:10][C:11]([NH2:13])=[O:12].[CH2:14]([O:16][C:17](=[O:22])[CH2:18][C:19]([CH3:21])=O)[CH3:15].B(F)(F)F.CCOCC.C(O)(=O)C>C1COCC1.C1(C)C=CC=CC=1.Cl[Cu]>[F:1][C:2]1[CH:9]=[CH:8][CH:7]=[CH:6][C:3]=1[CH:4]1[C:18]([C:17]([O:16][CH2:14][CH3:15])=[O:22])=[C:19]([CH3:21])[NH:13][C:11](=[O:12])[NH:10]1

Participants

9

Reactant 5

HCID 176Acetic AcidHCID 1176UreaHCID 8000Boron trifluoride etherateHCID 8868Ethyl AcetoacetateHCID 67970o-Fluorobenzaldehyde

Product 1

HCID 2831294Ethyl 4-(2-fluorophenyl)-6-methyl-2-oxo-1,2,3,4-tetrahydropyrimidine-5-carboxylateYield 88.3%

Reagents, catalysts & solvents 3

HCID 62652Cuprous chlorideCatalystHCID 1140TolueneSolventHCID 8028TetrahydrofuranSolvent

Procedure

A mixture of 2-fluorobenzaldehyde (5 g, 40.28 mmol), urea (3.8 g, 61 mmol), ethylacetoaceate (5.24 g, 40.28 mmol), CuCl (0.4 g, 4 mmol), BF3.OEt2 (7 mL, 53 mmol), and glacial acetic acid (0.24 g, 4 mmol) in THF (80 mL) was refluxed for 18 h and then cooled to room temperature. The mixture was quenched with saturated NaHCO3 (50 mL), and EtOAc (100 mL) was added. The layers were separated and the organic layer with a white suspension was evaporated to give a white solid. The solid was suspended in toluene (100 mL) and stirred for 2 days at room temperature. The solid was filtered, washed with ether, and dried to give ethyl 4-(2-fluorophenyl)-1,2,3,4-tetrahydro-6-methyl-2-oxopyrimidine-5-carboxylate (9.9 g, 88%). Mass Spec. FIA MS 279 (M+1).

Workup

  1. temperaturewas refluxed for 18 h
  2. customThe mixture was quenched with saturated NaHCO3 (50 mL), and EtOAc (100 mL)
  3. additionwas added
  4. customThe layers were separated
  5. customthe organic layer with a white suspension was evaporated
  6. customto give a white solid
  7. filtrationThe solid was filtered
  8. washwashed with ether
  9. customdried

Sources & evidence

ORD record
ord-c363b8bdd26847728bb630c3fa08ea34
Source dataset
uspto-grants-2013_10
Patent number
US08546414B2

Reaction notes

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