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

HRID 38676

Reaction equation

HRID 38676 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)propanoate

Reagents, catalysts & solvents 1

HCID 6342AcetonitrileSolvent

Procedure

A suspension of 3,5-dimethyl-1H-pyrazole (Aldrich, 8 g, 0.083 mol), anhydrous K2CO3 (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, so 0.2 equivalents of K2CO3 were added to the mixture which was refluxed over weekend. Reaction was checked, starting material was still detected. 0.2 eq. of K2CO3 were added to the mixture, which was refluxed during 24 h. Reaction was stopped, no advances were observed. 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 by chromatographic column 70 g cartridge (ISOLUTE silica) using Hex/EtOAc 100/0 to 20/80 giving (11.6 g 71%) 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. additionwere added to the mixture which
  4. temperaturewas refluxed over weekend
  5. customReaction
  6. temperaturewas refluxed during 24 h
  7. customReaction
  8. customReaction mixture
  9. filtrationwas filtered
  10. customSolvent was evaporated under reduced pressure
  11. additionResidue was diluted with 50 ml of DCM
  12. washwashed with water
  13. customOrganic layer was separated
  14. extractionaqueous fraction was extracted three times with 70 mL of DCM
  15. washCombined organic extracts were washed with brine
  16. dry with materialdried over Na2SO4 (anh)
  17. filtrationfiltered
  18. concentrationconcentrated
  19. customResidue was purified by chromatographic column 70 g cartridge (ISOLUTE silica)

Sources & evidence

ORD record
ord-22c27cacdc74464198a9ab92f9f8da1e
Source dataset
uspto-grants-2013_09
Patent number
US08524750B2

Linked notes

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