Triethylamine → HCID 58074949, compound

HRID 655778Notes

Reaction equation

HRID 655778 reaction equation
[Cl:1][C:2]1[N:3]=[CH:4][C:5]([C:8]([OH:10])=O)=[N:6][CH:7]=1.[C:11]([O:17][CH2:18][CH3:19])(=[O:16])[CH2:12]C(O)=O.C[Mg]Br.C(N(CC)CC)C>S(Cl)(Cl)=O.O1CCCC1>[Cl:1][C:2]1[N:3]=[CH:4][C:5]([C:8](=[O:10])[CH2:12][C:11]([O:17][CH2:18][CH3:19])=[O:16])=[N:6][CH:7]=1

Participants

7

Reactant 4

HCID 8471TriethylamineHCID 70615Monoethyl malonateHCID 4654725-Chloropyrazinoic acid2×HCID 178418573HCID 178418573, compound

Product 1

HCID 58074949HCID 58074949, compoundYield 53.16%

Reagents, catalysts & solvents 2

HCID 8028TetrahydrofuranSolvent2×HCID 24386Thionyl ChlorideSolvent

Conditions

Temperature
0 °C

Procedure

5-Chloropyrazine-2-carboxylic acid (Intermediate 44, 21 g, 0.132 mol) was taken in thionyl chloride (100 mL) which was heated to reflux for 2 h and excess thionyl chloride was distilled off under reduced pressure to obtain a residue, which was dissolved in dry tetrahydrofuran (100 mL). In another round bottom flask ethyl hydrogen malonoate (15.8 g, 0.132 mol) was dissolved in tetrahydrofuran (500 mL) which was cooled to 0° C. To the resulting solution was added methyl magnesium bromide (88 mL, 0.265 M) and stirred the reaction mixture was stirred for 30 min before triethylamine (39.9 g, 0.396 M) was added. To this reaction mixture the above prepared acid chloride mixture was added, stirred for 2 h at room temperature and tetrahydrofuran was evaporated from the reaction mixture and the water (500 mL) was added and extracted with ethyl acetate (2×200 mL). The organic layers were combined and dried over anhydrous sodium sulphate, concentrated under reduced pressure to get obtain crude product which was purified by flash column chromatography (10% ethyl acetate/pet ether) to afford 16.0 g (53.16%) of ethyl 3-(5-chloropyrazin-2-yl)-3-oxopropanoate white solid.

Workup

  1. temperaturewas heated
  2. temperatureto reflux for 2 h
  3. distillationexcess thionyl chloride was distilled off under reduced pressure
  4. customto obtain a residue, which
  5. additionwas added
  6. additionwas added
  7. stirringstirred for 2 h at room temperature
  8. customtetrahydrofuran was evaporated from the reaction mixture
  9. additionthe water (500 mL) was added
  10. extractionextracted with ethyl acetate (2×200 mL)
  11. dry with materialdried over anhydrous sodium sulphate
  12. concentrationconcentrated under reduced pressure
  13. customto get
  14. customobtain crude product which
  15. customwas purified by flash column chromatography (10% ethyl acetate/pet ether)

Sources & evidence

ORD record
ord-5d7d72211807406ab053cc7a510b0434
Source dataset
uspto-grants-2011_12
Patent number
US08071605B2

Reaction notes

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