Isopropyl3-aminocrotonate → Isopropyl 2-methoxyethyl 4-(2-fluorophenyl)-1,4-dihydro-2,6-dimethylpyridine-3,5-dicarboxylate

HRID 987009Notes

Reaction equation

HRID 987009 reaction equation
[C:1]([C:4](=[CH:12][C:13]1[CH:18]=[CH:17][CH:16]=[CH:15][C:14]=1[F:19])[C:5]([O:7][CH2:8][CH2:9][O:10][CH3:11])=[O:6])(=O)[CH3:2].[NH2:20][C:21]([CH3:29])=[CH:22][C:23]([O:25][CH:26]([CH3:28])[CH3:27])=[O:24].C1(C)C=CC=CC=1.C(OCC)(=O)C>C(O)(C)C>[F:19][C:14]1[CH:15]=[CH:16][CH:17]=[CH:18][C:13]=1[CH:12]1[C:4]([C:5]([O:7][CH2:8][CH2:9][O:10][CH3:11])=[O:6])=[C:1]([CH3:2])[NH:20][C:21]([CH3:29])=[C:22]1[C:23]([O:25][CH:26]([CH3:28])[CH3:27])=[O:24]

Participants

5

Reactant 3

HCID 3271821Isopropyl3-aminocrotonateHCID 21584019Toluene ethylacetateHCID 599577782-Methoxyethyl 2-acetyl-3-(2-fluorophenyl)-2-propenoate

Product 1

HCID 15295381Isopropyl 2-methoxyethyl 4-(2-fluorophenyl)-1,4-dihydro-2,6-dimethylpyridine-3,5-dicarboxylateYield 48%

Reagents, catalysts & solvents 1

HCID 3776IsopropanolSolvent

Procedure

4.0 g (about 15 mmol) of the compound from Example I are heated to reflux overnight in 100 ml of isopropanol with 2.2 g (15 mmol) of isopropyl 3-amino-2-butenoate. After thin-layer chromatographic checking (SiO2, toluene/ethyl acetate 5:1) shows complete conversion, the reaction mixture is concentrated, the residue is taken up with toluene, the solution is concentrated again and the residue is then purified by filtration on silica gel (eluent: toluene/ethyl acetate 100:1-5:1). A crystallizing yellow oil is obtained, which is recrystallized from methanol at about −15° C. 2.8 g (48%) of the target compound are obtained.

Workup

  1. concentrationthe reaction mixture is concentrated
  2. concentrationthe solution is concentrated again
  3. filtrationthe residue is then purified by filtration on silica gel (eluent: toluene/ethyl acetate 100:1-5:1)
  4. customA crystallizing yellow oil is obtained
  5. customwhich is recrystallized from methanol at about −15° C

Sources & evidence

ORD record
ord-10106c774ecb41e2a1b1683c35aac6d4
Source dataset
uspto-grants-2003_10
Patent number
US06630494B2

Reaction notes

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