Potassium tert-butoxide → Propyl 5-cyano-2-methyl-4-(2-methyl-4-oxo-4H-chromen-8-yl)-6-(trifluoromethyl)-1,4-dihydropyridine-3-carboxylate

HRID 557417Notes

Reaction equation

HRID 557417 reaction equation
[CH3:1][C:2]1[O:3][C:4]2[C:9]([C:10](=[O:12])[CH:11]=1)=[CH:8][CH:7]=[CH:6][C:5]=2[CH:13]=[C:14]([C:21](=O)[CH3:22])[C:15]([O:17][CH2:18][CH2:19][CH3:20])=[O:16].[NH2:24][C:25]([C:29]([F:32])([F:31])[F:30])=[CH:26][C:27]#[N:28].CC(C)([O-])C.[K+]>CC(O)C>[C:27]([C:26]1[CH:13]([C:5]2[CH:6]=[CH:7][CH:8]=[C:9]3[C:4]=2[O:3][C:2]([CH3:1])=[CH:11][C:10]3=[O:12])[C:14]([C:15]([O:17][CH2:18][CH2:19][CH3:20])=[O:16])=[C:21]([CH3:22])[NH:24][C:25]=1[C:29]([F:32])([F:31])[F:30])#[N:28]

Participants

5

Reactant 3

HCID 23665647Potassium tert-butoxideHCID 534010963-Amino-4,4,4-trifluorobut-2-enenitrileHCID 66991694Propyl 2-[(2-methyl-4-oxo-4H-chromen-8-yl)methylene]-3-oxobutanoate

Product 1

HCID 66991500Propyl 5-cyano-2-methyl-4-(2-methyl-4-oxo-4H-chromen-8-yl)-6-(trifluoromethyl)-1,4-dihydropyridine-3-carboxylate

Reagents, catalysts & solvents 1

HCID 3776IsopropanolSolvent

Procedure

A solution of 295 mg (0.94 mmol) of propyl 2-[(2-methyl-4-oxo-4H-chromen-8-yl)methylene]-3-oxobutanoate in 20 ml of 2-propanol is mixed with 127.71 mg (0.94 mmol) of 3-amino-4,4,4-trifluorobut-2-enenitrile [preparation in analogy to K. Krespan, J. Org. Chem. 34, 4245 (1969)] and 15.8 mg (0.14 mmol) of potassium tert-butoxide and stirred under reflux for 12 h. After cooling, the mixture is concentrated. The residue is purified on an Analogix cartridge (F12M) (mobile phase: cyclohexane/ethyl acetate 2:1). After concentration of the product fractions, the residue is crystallized from diethyl ether. 88.4 mg (20.7% of theory) of the title compound are obtained as white crystals.

Workup

  1. temperatureunder reflux for 12 h
  2. temperatureAfter cooling
  3. concentrationthe mixture is concentrated
  4. customThe residue is purified on an Analogix cartridge (F12M) (mobile phase: cyclohexane/ethyl acetate 2:1)
  5. customAfter concentration of the product fractions, the residue is crystallized from diethyl ether

Sources & evidence

ORD record
ord-ad92ec7c812f4358a8903563414644df
Source dataset
uspto-grants-2011_11
Patent number
US08058447B2

Reaction notes

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