Hydrochloric Acid → Methyl 1,4,5,7-tetrahydro-4-(4-chlorophenyl)-2-methyl-5-oxo-furo[3,4-b]-pyridine-3-carboxylate

HRID 636534Notes

Reaction equation

HRID 636534 reaction equation
[Cl:1][C:2]1[CH:9]=[CH:8][C:5]([CH:6]=O)=[CH:4][CH:3]=1.C(O[CH2:14][C:15](=O)[CH2:16][C:17]([O:19][CH2:20]C)=[O:18])(=O)C.[NH2:23]/[C:24](/[CH3:30])=[CH:25]\[C:26]([O:28]C)=[O:27].Cl>C(O)(C)C>[Cl:1][C:2]1[CH:9]=[CH:8][C:5]([CH:6]2[C:16]([C:17]([O:19][CH3:20])=[O:18])=[C:15]([CH3:14])[NH:23][C:24]3[CH2:30][O:28][C:26](=[O:27])[C:25]2=3)=[CH:4][CH:3]=1

Participants

6

Reactant 4

HCID 313Hydrochloric AcidHCID 77264-ChlorobenzaldehydeHCID 643918Methyl 3-aminocrotonateHCID 11480907Ethyl 4-acetoxyacetoacetate

Product 1

HCID 21255217Methyl 1,4,5,7-tetrahydro-4-(4-chlorophenyl)-2-methyl-5-oxo-furo[3,4-b]-pyridine-3-carboxylate

Reagents, catalysts & solvents 1

HCID 3776IsopropanolSolvent

Procedure

3 g (21.3 mmol) of 4-chlorobenzaldehyde, 4.0 g (21.3 mmol) of ethyl 4-acetoxyacetoacetate and 2.5 g (21.3 mmol) of methyl 3-aminocrotonate are dissolved in 40 ml of isopropanol and heated to reflux for 12 h. The mixture is then treated with 10 ml of dilute aqueous HCl and heated to reflux for a further 30 min. The mixture is partitioned between toluene and water. Drying (MgSO4) and concentration of the organic phase yields a white solid which is purified by filtration through 50 g of silica gel (ethyl acetate/petroleum ether 1+1) and subsequent recrystallization from ethyl acetate/petroleum ether. 2.6 g (8.13 mmol, 38%) are obtained.

Workup

  1. temperatureheated
  2. temperatureto reflux for 12 h
  3. temperatureheated
  4. temperatureto reflux for a further 30 min
  5. customThe mixture is partitioned between toluene and water
  6. dry with materialDrying (MgSO4) and concentration of the organic phase
  7. customyields a white solid which
  8. filtrationis purified by filtration through 50 g of silica gel (ethyl acetate/petroleum ether 1+1) and subsequent recrystallization from ethyl acetate/petroleum ether
  9. custom2.6 g (8.13 mmol, 38%) are obtained

Sources & evidence

ORD record
ord-dd512865b5444fb2a48bef59e4b99114
Source dataset
uspto-grants-2001_02
Patent number
US06194428B1

Reaction notes

Loading…