Hydrochloric Acid → Ethyl 3-(methoxycarbonyl)-β-oxobenzenepropanoate

HRID 896067Notes

Reaction equation

HRID 896067 reaction equation
[C:1]([O:12][CH3:13])(=[O:11])[C:2]1[CH:10]=[CH:9][CH:8]=[C:4]([C:5]([O-:7])=O)[CH:3]=1.C(N1C=CN=C1)(N1C=CN=C1)=[O:15].[K].[Cl-].[Mg+2].[Cl-].C(N(CC)CC)C.Cl.[O:38]1[CH2:42][CH2:41][CH2:40][CH2:39]1>ClCCl.C(OCC)(=O)CC([O-])=O.C(#N)C>[CH2:39]([O:38][C:42](=[O:15])[CH2:41][C:5]([C:4]1[CH:8]=[CH:9][CH:10]=[C:2]([C:1]([O:12][CH3:13])=[O:11])[CH:3]=1)=[O:7])[CH3:40]

Participants

11

Reactant 7

HCID 313Hydrochloric AcidHCID 8028TetrahydrofuranHCID 8471TriethylamineHCID 682631,1'-CarbonyldiimidazoleHCID 5360315Magnesium ChlorideHCID 5462222PotassiumHCID 69512791,3-Benzenedicarboxylic acid, monomethyl ester

Product 1

HCID 20814236Ethyl 3-(methoxycarbonyl)-β-oxobenzenepropanoate

Reagents, catalysts & solvents 3

HCID 6342AcetonitrileSolventHCID 6344DichloromethaneSolventHCID 3595298Propanedioic acid, monoethyl esterSolvent

Procedure

Monomethyl isophathalate (2.0 g, 11.1 mmol) was dissolved in a 1:3 mixture of tetrahydrofuran and dichloromethane. Carbonyldiimidazole (1.89 g, 11.7 mmol) was added slowly. The mixture was then stirred under nitrogen for 1 hr at room temperature. In a separate flask, ethyl malonate, potassium salt (3.96 g, 23.3 mmol) was dissolved in acetonitrile and magnesium chloride (2.64 g, 27.8 mmol) and triethylamine (4.95 ml, 35.5 mmol) was added to result in a heterogeneous suspension, which was stirred at room temperature for 1 h. The two reaction mixtures were mixed, and the resulting suspension was stirred @80° C. for 8 hours. 100 ml of a 2N aqueous HCl solution was added to the reaction mixture, which was subsequently extracted with dichloromethane. The organic layer was washed with 2N HCl twice and twice with water, dried (MgSO4) and evaporated in vacuo to afford 4.0 g of an oil. Purification on silica gel using Biotage® eluting with 20% EtOAc in Hexanes, recovered 1.5 g of 6A as a clear oil. LC/MS: Retention Time=1.38 min (YMC S5 Turbopack 4.6×33mm, 2 min gradient; Solvent A=10% MeOH, 90% H2O, 0.1% TFA; Solvent B=90% MeOH, 10% H2O, 0.1% TFA) with a (M+H)+=251.13. 1H-NMR (Joel 500 Hz/ CDCl3) (1:2 mixture of enol and keto form) Keto: δ 1.17-1.21 (t, 3H, J=8.8 Hz), 3.89 (s, 3H), 3.96 (s, 2H), 4.12-4.18 (q, 2H, J=8.8 Hz) 5.67(s, 1H); 7.50-7.54 (t, 1H, J=9.3 Hz), 8.07-8.09 (d, 1H, J=9.9 Hz), 8.19-8.21 (d, 1H, J=9.9 Hz), 8.5 (d, 1H, J=2.2 Hz)

Workup

  1. customto result in a heterogeneous suspension, which
  2. stirringwas stirred at room temperature for 1 h
  3. customThe two reaction mixtures
  4. additionwere mixed
  5. stirringthe resulting suspension was stirred @80° C. for 8 hours
  6. extractionwas subsequently extracted with dichloromethane
  7. washThe organic layer was washed with 2N HCl twice
  8. dry with materialtwice with water, dried (MgSO4)
  9. customevaporated in vacuo

Sources & evidence

ORD record
ord-68a7cdd5c62046d79e27c073462233b8
Source dataset
uspto-grants-2005_07
Patent number
US06919335B2

Reaction notes

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