Triethylamine → HCID 66846757, compound

HRID 1466639Notes

Reaction equation

HRID 1466639 reaction equation
[CH2:1]([O:3][C:4](=[O:9])[CH2:5][C:6]([O-:8])=O)[CH3:2].[K+].C(N(CC)CC)C.[Mg+2].[Cl-].[Cl-].[Cl:21][C:22]1[CH:23]=[CH:24][C:25]([O:31][CH:32]2[CH2:34][CH2:33]2)=[C:26]([CH:30]=1)C(Cl)=O>C(#N)C>[Cl:21][C:22]1[CH:23]=[CH:24][C:25]([O:31][CH:32]2[CH2:34][CH2:33]2)=[C:26]([C:6](=[O:8])[CH2:5][C:4]([O:3][CH2:1][CH3:2])=[O:9])[CH:30]=1

Participants

6

Reactant 4

HCID 8471Triethylamine2×HCID 3446434Potassium ethyl malonateHCID 5360315Magnesium ChlorideHCID 86668386HCID 86668386, compound

Product 1

HCID 66846757HCID 66846757, compoundYield 88.6%

Reagents, catalysts & solvents 1

HCID 6342AcetonitrileSolvent

Conditions

Temperature
0 °C

Procedure

Acetonitrile (200 mL) was added to potassium 3-ethoxy-3-oxopropanoate (31.1 g, 182.7 mmol), in a 1000 mL 3-necked flask under N2 with stirring. The reaction mixture was cooled to 0° C., then triethylamine (38.8 mL, 278.4 mmol) was added, followed by MgCl2 (20.71 g, 217.5 mmol). The reaction mixture was warmed to room temperature and stirred for an additional 2.5 h. The resulting slurry was cooled to 0° C. and 5-chloro-2-cyclopropoxybenzoyl chloride (18.5 g, 87 mmol) was added dropwise followed by the addition of more triethylamine (3.9 mL, 28 mmol). The mixture was stirred at room temperature overnight, then concentrated in vacuo. 1 L of toluene was added, the mixture was cooled to 0° C., then 125 mL of HCl (13% aqueous solution) was added. The ice bath was removed, the mixture was stirred for 30 minutes, then the layers were separated and the organics washed with water and evaporated to dryness. The residue was purified by silica gel chromatography (Hexanes/EtOAc=3:1) to afford 21.8 g of ethyl 3-(5-chloro-2-cyclopropoxyphenyl)-3-oxopropanoate. LCMS (ESI) m+H=283.0; 1H NMR (400 MHz, CDCl3) δ: 7.81 (t, 1H), 7.44 (dd, 1H), 7.29 (d, 1H), 4.24 (m, 2H), 3.87 (s, 2H), 3.78 (m, 1H), 1.23 (t, 2H), 0.85 (m, 4H).

Workup

  1. temperatureThe reaction mixture was warmed to room temperature
  2. stirringstirred for an additional 2.5 h
  3. temperatureThe resulting slurry was cooled to 0° C.
  4. stirringThe mixture was stirred at room temperature overnight
  5. concentrationconcentrated in vacuo
  6. addition1 L of toluene was added
  7. temperaturethe mixture was cooled to 0° C.
  8. addition125 mL of HCl (13% aqueous solution) was added
  9. customThe ice bath was removed
  10. stirringthe mixture was stirred for 30 minutes
  11. customthe layers were separated
  12. washthe organics washed with water
  13. customevaporated to dryness
  14. customThe residue was purified by silica gel chromatography (Hexanes/EtOAc=3:1)

Sources & evidence

ORD record
ord-26ea0f2ea7f94f8197a27bd7020ca801
Source dataset
uspto-grants-2015_04
Patent number
US08999998B2

Reaction notes

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