Isopropyl3-aminocrotonate → 3-Methyl 5-(1-methylethyl) 4-(3-chloro-6-fluoro-2-(trifluoromethyl)phenyl)-2-(fluoromethyl)-1,4-dihydro-6-methyl-3,5-pyridinedicarboxylate

HRID 1789011Notes

Reaction equation

HRID 1789011 reaction equation
[Cl:1][C:2]1[C:3]([C:11]([F:14])([F:13])[F:12])=[C:4]([C:7]([F:10])=[CH:8][CH:9]=1)[CH:5]=O.[F:15][CH2:16][C:17](=O)[CH2:18][C:19]([O:21][CH3:22])=[O:20].[NH2:24][C:25]([CH3:33])=[CH:26][C:27]([O:29][CH:30]([CH3:32])[CH3:31])=[O:28]>>[Cl:1][C:2]1[C:3]([C:11]([F:14])([F:13])[F:12])=[C:4]([CH:5]2[C:26]([C:27]([O:29][CH:30]([CH3:32])[CH3:31])=[O:28])=[C:25]([CH3:33])[NH:24][C:17]([CH2:16][F:15])=[C:18]2[C:19]([O:21][CH3:22])=[O:20])[C:7]([F:10])=[CH:8][CH:9]=1

Participants

4

Reactant 3

HCID 3271821Isopropyl3-aminocrotonateHCID 14170515Methyl 4-fluoro-3-oxobutanoateHCID 141705223-Chloro-6-fluoro-2-(trifluoromethyl)benzaldehyde

Product 1

HCID 1253293-Methyl 5-(1-methylethyl) 4-(3-chloro-6-fluoro-2-(trifluoromethyl)phenyl)-2-(fluoromethyl)-1,4-dihydro-6-methyl-3,5-pyridinedicarboxylateYield 7.5%

Procedure

3-Chloro-6-fluoro-2-(trifluoromethyl)benzaldehyde (1.3 g, 5.7 mmoles), methyl 4-fluoro-3-oxobutanoate (0.77 g, 5.7 mmoles) and 1-methylethyl 3-amino-2-butenoate (0.82 g, 5.7 mmoles) were heated under nitrogen with stirring for 1.5 hours at 90°, followed by 1.5 hours at 100° and then 1 hour at 110°. The cooled reaction mixture was chromatographed twice on silica first using methylene chloride as eluent and then toluene/ethyl acetate mixtures. The title compound (0.2 g) was obtained after crystallisation from petroleum ether (60°-80°) mp 142°-3°.

Workup

  1. waitfollowed by 1.5 hours at 100°
  2. custom1 hour
  3. customat 110°
  4. customThe cooled reaction mixture
  5. customwas chromatographed twice on silica first using methylene chloride as eluent

Sources & evidence

ORD record
ord-ae8bbf4cd8384c3382f6799f2cf7e2e9
Source dataset
uspto-grants-1987_08
Patent number
US04686217

Reaction notes

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