Dimedone → Ethyl 7,7-dimethyl-5-oxo-4-(5-phenylthiophen-2-yl)-2-propyl-1,4,5,6,7,8-hexahydroquinoline-3-carboxylate

HRID 1020278Notes

Reaction equation

HRID 1020278 reaction equation
[CH3:1][C:2]1([CH3:10])[CH2:9][C:7](=[O:8])[CH2:6][C:4](=O)[CH2:3]1.[C:11]1([C:17]2[S:21][C:20]([CH:22]=O)=[CH:19][CH:18]=2)[CH:16]=[CH:15][CH:14]=[CH:13][CH:12]=1.[CH2:24]([CH2:27][C:28](=O)[CH2:29][C:30]([O:32][CH2:33][CH3:34])=[O:31])[CH2:25]C.C([O-])(=O)C.[NH4+:40]>C(O)C.C(OCC)(=O)C>[CH3:10][C:2]1([CH3:1])[CH2:3][C:4]2[NH:40][C:28]([CH2:27][CH2:24][CH3:25])=[C:29]([C:30]([O:32][CH2:33][CH3:34])=[O:31])[CH:22]([C:20]3[S:21][C:17]([C:11]4[CH:12]=[CH:13][CH:14]=[CH:15][CH:16]=4)=[CH:18][CH:19]=3)[C:6]=2[C:7](=[O:8])[CH2:9]1

Participants

7

Reactant 4

HCID 31358DimedoneHCID 1770535-Phenylthiophene-2-carbaldehydeHCID 517165Ammonium AcetateHCID 559036Ethyl 3-oxoheptanoate

Product 1

HCID 44136863Ethyl 7,7-dimethyl-5-oxo-4-(5-phenylthiophen-2-yl)-2-propyl-1,4,5,6,7,8-hexahydroquinoline-3-carboxylateYield 68.5%

Reagents, catalysts & solvents 2

HCID 702EthanolSolventHCID 8857Ethyl AcetateSolvent

Procedure

To a solution of dimedone (0.70 g, 5.0 mmole) in hot ethanol (15 ml) was added 5-phenyl-2-thiophenecarboxaldehyde (0.940 g, 5.0 mmole), ethyl propylacetoacetate (0.80 ml, 5.0 mmole) and lastly ammonium acetate (0.770 g, 10.0 mmole). The mixture was held at reflux for 48 h. No precipitate was observed. The ethanol was removed in vacuo to provide a crude viscous material which was subjected to a 100 g SiO2 flash column using 40% ethyl acetate:hexanes as eluent. The desired product (1.54 g, 68%) was obtained as a yellow amorphous solid. Rf=0.37 in 1:1 ethyl acetate hexanes. 1H NMR (400 MHz; CDCl3) d 7.5 (bd, 2H, J=7.0 Hz); 7.32-7.25 (m, 2H); 7.19 (at, 1H, J=7.4 Hz); 7.04 (d, 1H, J=7.4 Hz); 6.8 (d, 1H, J=3.5 Hz); 6.38 (bs, 1H); 5.41 (s, 1H); 4.22-3.90 (m, 2H); 2.90-2.80 (m, 1H); 2.72-2.63 (m, 1H); 2.35 (d, 1H, J=16.8 Hz); 2.25 (d, 1H, J=16.8 Hz); 2.3-2.2 (On, 2H); 1.74-1.62 (m, 2H); 1.25 (at, 3H, J=7.0 Hz); 1.07 (s, 3H); 1.02 (s, 3H); 1.01 (at, 3H, J=7.0 Hz); 1.05-0.95 (m, 2H). LC MS shows MH+ at 450; 2M+H at 899 and 2M+Na at 921.

Workup

  1. temperatureat reflux for 48 h
  2. customThe ethanol was removed in vacuo
  3. customto provide a crude viscous material which

Sources & evidence

ORD record
ord-413fb2d6373d4677baa89c69490d54cc
Source dataset
uspto-grants-2014_05
Patent number
US08716319B2

Reaction notes

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