Methyl 4-(trifluoromethyl)benzoylacetate → Methyl 2-ethyl-4-oxo-6-[4-(trifluoromethyl)phenyl]-1,4-dihydropyridine-3-carboxylate

HRID 1099593Notes

Reaction equation

HRID 1099593 reaction equation
O=[C:2]([C:8]1[CH:13]=[CH:12][C:11]([C:14]([F:17])([F:16])[F:15])=[CH:10][CH:9]=1)[CH2:3][C:4]([O:6]C)=O.[NH2:18][C:19]([CH2:25][CH3:26])=[CH:20][C:21]([O:23][CH3:24])=[O:22]>C1(C)C(C)=CC=CC=1>[CH2:25]([C:19]1[NH:18][C:2]([C:8]2[CH:13]=[CH:12][C:11]([C:14]([F:17])([F:16])[F:15])=[CH:10][CH:9]=2)=[CH:3][C:4](=[O:6])[C:20]=1[C:21]([O:23][CH3:24])=[O:22])[CH3:26]

Participants

4

Reactant 2

HCID 735882Methyl 4-(trifluoromethyl)benzoylacetateHCID 57860398Methyl 3-aminopent-2-enoate

Product 1

HCID 59487341Methyl 2-ethyl-4-oxo-6-[4-(trifluoromethyl)phenyl]-1,4-dihydropyridine-3-carboxylate

Reagents, catalysts & solvents 1

HCID 7237O-XyleneSolvent

Procedure

1.00 g (3.84 mmol) of methyl 3-oxo-3-[4-(trifluoromethyl)phenyl]propanoate and 546 mg (4.23 mmol) of methyl 3-aminopent-2-enoate [Pena et al., J. Am. Chem. Soc. 124., 14552-14553 (2002)] were taken up in 4 ml of xylene, 1.50 g molecular sieve (4 Å) which had been dried by heating were added and the mixture was reacted at reflux temperature overnight. The molecular sieve was removed by filtration and washed with methanol/chloroform (1/1). The combined organic phases were concentrated on a rotary evaporator and the crude product was purified by preparative HPLC (mobile phase: acetonitrile/water, gradient 10:90→90:10). This gave 270 mg (21% of theory) of the target compound.

Workup

  1. custom1.50 g molecular sieve (4 Å) which had been dried
  2. temperatureby heating
  3. additionwere added
  4. customthe mixture was reacted
  5. temperatureat reflux temperature overnight
  6. customThe molecular sieve was removed by filtration
  7. washwashed with methanol/chloroform (1/1)
  8. concentrationThe combined organic phases were concentrated on a rotary evaporator
  9. customthe crude product was purified by preparative HPLC (mobile phase: acetonitrile/water, gradient 10:90→90:10)

Sources & evidence

ORD record
ord-826c7462aac94f5b9dd78a986b4e294c
Source dataset
uspto-grants-2012_03
Patent number
US08143411B2

Reaction notes

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