Iodine → ethyl 2-(3,5-dimethyl-1H-pyrazol-1-yl)propanoate

HRID 522619Notes

Reaction equation

HRID 522619 reaction equation
[CH3:1][C:2]1[CH:6]=[C:5]([CH3:7])[NH:4][N:3]=1.C([O-])([O-])=O.[K+].[K+].Br[CH:15]([CH3:21])[C:16]([O:18][CH2:19][CH3:20])=[O:17].II>C(#N)C>[CH3:1][C:2]1[CH:6]=[C:5]([CH3:7])[N:4]([CH:15]([CH3:21])[C:16]([O:18][CH2:19][CH3:20])=[O:17])[N:3]=1

Participants

6

Reactant 4

HCID 807IodineHCID 62103,5-DimethylpyrazoleHCID 11430Potassium Carbonate3×HCID 79040Ethyl 2-bromopropionate

Product 1

HCID 12008675ethyl 2-(3,5-dimethyl-1H-pyrazol-1-yl)propanoateYield 71.2%

Reagents, catalysts & solvents 1

HCID 6342AcetonitrileSolvent

Procedure

A suspension of 3,5-dimethyl-1H-pyrazole (ALDRICH, 8 g, 0.083 mol), anhydrous K2CO3 (ALDRICH, 11.50 g, 0.083 mol) and ethyl 2-bromopropanoate (ALDRICH, 15 g, 0.083 mol) in 50 mL of dry ACN was refluxed with mechanical stirring for 24 h. Reaction was checked by TLC (iodine), and starting material was detected. 0.2 equivalents of K2CO3 were added to the mixture which was refluxed over the weekend. Reaction was checked, starting material was still detected. 0.2 eq. of K2CO3 were added to the mixture, which was refluxed during 24 additional hours. Reaction mixture was filtered. Solvent was evaporated under reduced pressure. Residue was diluted with 50 ml of DCM, and washed with water. Organic layer was separated and aqueous fraction was extracted three times with 70 mL of DCM. Combined organic extracts were washed with brine, dried over Na2SO4 (anh), filtered and concentrated under reduce pressure. Residue was purified using a 70 g silica gel cartridge with a linear gradient of hexane/EtOAc 100/0 to 20/80 to yield the title compound (11.6 g 71%) as colourless oil. 1H NMR (300 MHz, CDCl3) δ ppm: 5.83 (s, 1H), 4.85 (q, 1H), 4.08-4.25 (m, 2H), 2.22-2.23 (m, 6H), 1.79 (d, 3H), 1.23 (t, 3H).

Workup

  1. temperaturewas refluxed
  2. customReaction
  3. temperaturewas refluxed over the weekend
  4. customReaction
  5. temperaturewas refluxed during 24 additional hours
  6. customReaction mixture
  7. filtrationwas filtered
  8. customSolvent was evaporated under reduced pressure
  9. additionResidue was diluted with 50 ml of DCM
  10. washwashed with water
  11. customOrganic layer was separated
  12. extractionaqueous fraction was extracted three times with 70 mL of DCM
  13. washCombined organic extracts were washed with brine
  14. dry with materialdried over Na2SO4 (anh)
  15. filtrationfiltered
  16. concentrationconcentrated
  17. customResidue was purified

Sources & evidence

ORD record
ord-13f8d64d703d4d508abfc6df7ee1d074
Source dataset
uspto-grants-2016_05
Patent number
US09334265B2

Reaction notes

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