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

HRID 2167308Notes

Reaction equation

HRID 2167308 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) δ 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 (m, 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-3d35c170993f4b1abcba3ced123b6696
Source dataset
uspto-grants-2015_06
Patent number
US09045428B2

Reaction notes

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