Toluene ethylacetate → 2-Cyanoethyl cyclopentyl 4-(2-chloro-6-fluorophenyl)-1,4-dihydro-2,6-dimethylpyridine-3,5-dicarboxylate

HRID 1108296Notes

Reaction equation

HRID 1108296 reaction equation
[C:1]([C:4](=[CH:13][C:14]1[C:19]([F:20])=[CH:18][CH:17]=[CH:16][C:15]=1[Cl:21])[C:5]([O:7][CH:8]1[CH2:12][CH2:11][CH2:10][CH2:9]1)=[O:6])(=O)[CH3:2].[NH2:22][C:23]([CH3:32])=[CH:24][C:25]([O:27][CH2:28][CH2:29][C:30]#[N:31])=[O:26].C1(C)C=CC=CC=1.C(OCC)(=O)C>C(O)(C)C>[Cl:21][C:15]1[CH:16]=[CH:17][CH:18]=[C:19]([F:20])[C:14]=1[CH:13]1[C:4]([C:5]([O:7][CH:8]2[CH2:12][CH2:11][CH2:10][CH2:9]2)=[O:6])=[C:1]([CH3:2])[NH:22][C:23]([CH3:32])=[C:24]1[C:25]([O:27][CH2:28][CH2:29][C:30]#[N:31])=[O:26]

Participants

5

Reactant 3

HCID 21584019Toluene ethylacetateHCID 53718049Cyclopentyl 2-acetyl-3-(2-chloro-6-fluorophenyl)-2-propenoateHCID 731858132-Cyanoethyl 3-amino-2-butenoate

Product 1

HCID 187848112-Cyanoethyl cyclopentyl 4-(2-chloro-6-fluorophenyl)-1,4-dihydro-2,6-dimethylpyridine-3,5-dicarboxylateYield 56.8%

Reagents, catalysts & solvents 1

HCID 3776IsopropanolSolvent

Procedure

280 g (0.63 mol) of cyclopentyl 2-acetyl-3-(2-chloro-6-fluorophenyl)-2-propenoate are dissolved with 97.2 g (0.63 mol) of 2-cyanoethyl 3-amino-2-butenoate in 400 ml of isopropanol and the solution is heated under reflux for about 8 hours until monitoring by thin layer chromatography (silica gel, toluene/ethyl acetate 5:1) shows complete conversion. The reaction mixture is concentrated and the residue is taken up twice more with toluene and the mixture concentrated again. Filtration twice over 2 l of silica gel each time using a toluene/ethyl acetate gradient gives 160 g of the target compound as an oil. A portion is further purified by chromatography over silica gel and crystallization from ether to give a crystalline solid of melting point 135-136° C.

Workup

  1. temperaturethe solution is heated
  2. concentrationThe reaction mixture is concentrated
  3. concentrationthe mixture concentrated again
  4. filtrationFiltration twice over 2 l of silica gel each time

Sources & evidence

ORD record
ord-0a53e95e384a46bfbad0de2eeaed7301
Source dataset
uspto-grants-2000_05
Patent number
US06066655

Reaction notes

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