Morpholine → (rac)-4-(4-Cyano-2-nitrophenyl)-6-methyl-2-oxo-1-[3-(trifluoromethyl)phenyl]-1,2,3,4-tetrahydropyrimidine-5-carboxylic acid

HRID 2064338Notes

Reaction equation

HRID 2064338 reaction equation
[C:1]([C:3]1[CH:8]=[CH:7][C:6]([CH:9]2[C:14]([C:15]([O:17]CC=C)=[O:16])=[C:13]([CH3:21])[N:12]([C:22]3[CH:27]=[CH:26][CH:25]=[C:24]([C:28]([F:31])([F:30])[F:29])[CH:23]=3)[C:11](=[O:32])[NH:10]2)=[C:5]([N+:33]([O-:35])=[O:34])[CH:4]=1)#[N:2].N1CCOCC1>C1COCC1.C1C=CC([P]([Pd]([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)[P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)=CC=1>[C:1]([C:3]1[CH:8]=[CH:7][C:6]([CH:9]2[C:14]([C:15]([OH:17])=[O:16])=[C:13]([CH3:21])[N:12]([C:22]3[CH:27]=[CH:26][CH:25]=[C:24]([C:28]([F:31])([F:29])[F:30])[CH:23]=3)[C:11](=[O:32])[NH:10]2)=[C:5]([N+:33]([O-:35])=[O:34])[CH:4]=1)#[N:2]

Participants

5

Reactant 2

HCID 8083MorpholineHCID 58133797(rac)-Allyl 4-(4-cyano-2-nitrophenyl)-6-methyl-2-oxo-1-[3-(trifluoromethyl)phenyl]-1,2,3,4-tetrahydropyrimidine-5-carboxylate

Product 1

HCID 58133686(rac)-4-(4-Cyano-2-nitrophenyl)-6-methyl-2-oxo-1-[3-(trifluoromethyl)phenyl]-1,2,3,4-tetrahydropyrimidine-5-carboxylic acid

Reagents, catalysts & solvents 2

HCID 178418397HCID 178418397, compoundCatalystHCID 8028TetrahydrofuranSolvent

Procedure

The reaction was carried out under argon. (rac)-Allyl 4-(4-cyano-2-nitrophenyl)-6-methyl-2-oxo-1-[3-(trifluoromethyl)phenyl]-1,2,3,4-tetrahydropyrimidine-5-carboxylate (15.0 g, 30.8 mmol) and morpholine (1.5 eq., 4.03 g, 46.3 mmol) were initially charged in dry THF (300 ml) at RT. The reaction mixture was degassed repeatedly (evacuation followed by venting with argon). Under protective gas, tetrakis(triphenylphosphine)palladium(0) (0.05 eq., 1.78 g, 1.54 mmol) was added, and the reaction mixture was stirred at RT for 2 h (HPLC control). The mixture was then concentrated, and the residue was taken up in ethyl acetate (700 ml). The organic phase was washed with 0.5 N hydrochloric acid (500 ml) and with saturated sodium chloride solution (300 ml), dried over sodium sulfate, filtered and concentrated under reduced pressure. The crude product was recrystallized from ethyl acetate and dried under high vacuum. The title compound was obtained as a solid (12.87 g, 93% of theory).

Workup

  1. customThe reaction mixture was degassed repeatedly (evacuation followed by venting with argon)
  2. concentrationThe mixture was then concentrated
  3. washThe organic phase was washed with 0.5 N hydrochloric acid (500 ml) and with saturated sodium chloride solution (300 ml)
  4. dry with materialdried over sodium sulfate
  5. filtrationfiltered
  6. concentrationconcentrated under reduced pressure
  7. customThe crude product was recrystallized from ethyl acetate
  8. customdried under high vacuum

Sources & evidence

ORD record
ord-49740c16f0e04d218cfbb0d69be99791
Source dataset
uspto-grants-2012_10
Patent number
US08288402B2

Reaction notes

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