Triethyl Phosphate → (rac)-Allyl 4-(4-cyano-2-nitrophenyl)-6-methyl-2-oxo-1-[3-(trifluoromethyl)phenyl]-1,2,3,4-tetrahydropyrimidine-5-carboxylate

HRID 2064337

Reaction equation

HRID 2064337 reaction equation
[C:1]([O:7][CH2:8][CH:9]=[CH2:10])(=[O:6])[CH2:2][C:3]([CH3:5])=O.[C:11]([C:13]1[CH:20]=[CH:19][C:16]([CH:17]=O)=[C:15]([N+:21]([O-:23])=[O:22])[CH:14]=1)#[N:12].[F:24][C:25]([F:37])([F:36])[C:26]1[CH:27]=[C:28]([NH:32][C:33]([NH2:35])=[O:34])[CH:29]=[CH:30][CH:31]=1.P(OCC)(OCC)(OCC)=O>C1COCC1.C(OCC)(=O)C>[CH2:8]([O:7][C:1]([C:2]1[CH:17]([C:16]2[CH:19]=[CH:20][C:13]([C:11]#[N:12])=[CH:14][C:15]=2[N+:21]([O-:23])=[O:22])[NH:35][C:33](=[O:34])[N:32]([C:28]2[CH:29]=[CH:30][CH:31]=[C:26]([C:25]([F:36])([F:37])[F:24])[CH:27]=2)[C:3]=1[CH3:5])=[O:6])[CH:9]=[CH2:10]

Participants

7

Reactant 4

HCID 6535Triethyl PhosphateHCID 25712(3-Trifluoromethylphenyl)ureaHCID 70701Allyl acetoacetateHCID 132385504-Formyl-3-nitrobenzonitrile

Product 1

HCID 58133797(rac)-Allyl 4-(4-cyano-2-nitrophenyl)-6-methyl-2-oxo-1-[3-(trifluoromethyl)phenyl]-1,2,3,4-tetrahydropyrimidine-5-carboxylate

Reagents, catalysts & solvents 2

HCID 8028TetrahydrofuranSolventHCID 8857Ethyl AcetateSolvent

Procedure

The reaction was carried out under argon. Allyl acetoacetate (5.94 g, 41.5 mmol; 1.0 eq.) was initially charged in THF (117 ml) at RT. Subsequently, 4-cyano-2-nitrobenzaldehyde (10.45 g, 41.5 mmol, purity 70%; 1.0 eq.), 1-[3-(trifluoromethyl)phenyl]urea (8.48 g, 41.5 mmol) and triethyl phosphate (17.7 g) were added. The mixture was stirred under reflux for 16 h. For work-up, initially ice-water was added, and the mixture was then taken up in ethyl acetate (400 ml). The organic phase was dried over solid sodium sulfate, filtered and concentrated under reduced pressure. The crude product was recrystallized from hot water/isopropanol (2:1, ˜400 ml). The solid obtained was triturated with diethyl ether (60 ml), once more filtered off with suction, washed with a little diethyl ether and dried under high vacuum. The title compound was obtained as a solid (16.63 g, 82% of theory).

Workup

  1. temperatureunder reflux for 16 h
  2. dry with materialThe organic phase was dried over solid sodium sulfate
  3. filtrationfiltered
  4. concentrationconcentrated under reduced pressure
  5. customThe crude product was recrystallized from hot water/isopropanol (2:1, ˜400 ml)
  6. customThe solid obtained
  7. customwas triturated with diethyl ether (60 ml)
  8. filtrationonce more filtered off with suction
  9. washwashed with a little diethyl ether
  10. customdried under high vacuum

Sources & evidence

ORD record
ord-f116b5aead5c44428e755d1c5c07cb97
Source dataset
uspto-grants-2012_10
Patent number
US08288402B2

Linked notes

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