Methyl 3-bromopropanoate → Methyl 3-[4-(3,5-dichlorobenzyl)-3,5-diethyl-1h-pyrazol-1-yl]propanoate

HRID 723597Notes

Reaction equation

HRID 723597 reaction equation
[Cl:1][C:2]1[CH:3]=[C:4]([CH:15]=[C:16]([Cl:18])[CH:17]=1)[CH2:5][C:6]1[C:7]([CH2:13][CH3:14])=[N:8][NH:9][C:10]=1[CH2:11][CH3:12].[O-]CC.[Na+].[CH3:23][O:24][C:25](=[O:29])[CH2:26][CH2:27]Br>C(O)C>[Cl:1][C:2]1[CH:3]=[C:4]([CH:15]=[C:16]([Cl:18])[CH:17]=1)[CH2:5][C:6]1[C:10]([CH2:11][CH3:12])=[N:9][N:8]([CH2:27][CH2:26][C:25]([O:24][CH3:23])=[O:29])[C:7]=1[CH2:13][CH3:14]

Participants

5

Reactant 3

HCID 76934Methyl 3-bromopropanoate2×HCID 2723922Sodium ethoxide2×HCID 98569994-(3,5-Dichlorobenzyl)-3,5-diethyl-1h-pyrazole

Product 1

HCID 10292504Methyl 3-[4-(3,5-dichlorobenzyl)-3,5-diethyl-1h-pyrazol-1-yl]propanoate

Reagents, catalysts & solvents 1

HCID 702EthanolSolvent

Procedure

A solution of the pyrazole of Example 11 (198 mg, 0.70 mmol) in ethanol (1 ml) was treated with sodium ethoxide (21% w/v in EtOH) (261 μL, 0.81 mmol) and then methyl-3-bromopropionate (153 μL, 1.40 mmol) and heated at 70° C. in a sealed Reacti-vial (Trade Mark) for 18 hours. Over a period of 3 days more sodium ethoxide (2.65 eq) and methyl-3-bromopropionate (6.0 eq) were added and the reaction was maintained under the same conditions. After cooling, the solution was concentrated under reduced pressure. The residue was partitioned between dichloromethane and water. The organic phase was dried over anhydrous magnesium sulphate, filtered and concentrated under reduced pressure. The crude material was purified by flash chromatography on silica gel eluting with pentane:ethyl acetate (5:1, by volume) to afford two products.

Workup

  1. temperaturethe reaction was maintained under the same conditions
  2. temperatureAfter cooling
  3. concentrationthe solution was concentrated under reduced pressure
  4. customThe residue was partitioned between dichloromethane and water
  5. dry with materialThe organic phase was dried over anhydrous magnesium sulphate
  6. filtrationfiltered
  7. concentrationconcentrated under reduced pressure
  8. customThe crude material was purified by flash chromatography on silica gel eluting with pentane:ethyl acetate (5:1, by volume)
  9. customto afford two products

Sources & evidence

ORD record
ord-726de1fb8c944d7fbc9f9430716678c5
Source dataset
uspto-grants-2006_11
Patent number
US07141585B2

Reaction notes

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