Ethylene carbonate → 2-(4-{1-[3-(Trifluoromethyl)-7,8-dihydro[1,2,4]triazolo[4,3-b]pyridazin-6-yl]piperidin-4-yl}phenoxy)ethanol

HRID 2381140Notes

Reaction equation

HRID 2381140 reaction equation
[O:1]1[CH2:5][CH2:4][O:3][C:2]1=O.[F:7][C:8]([F:32])([F:31])[C:9]1[N:13]2[N:14]=[C:15]([N:18]3[CH2:23][CH2:22][CH:21]([C:24]4[CH:29]=[CH:28]C(O)=[CH:26][CH:25]=4)[CH2:20][CH2:19]3)[CH2:16][CH2:17][C:12]2=[N:11][N:10]=1.C(=O)([O-])[O-].[K+].[K+]>CN(C=O)C>[F:32][C:8]([F:7])([F:31])[C:9]1[N:13]2[N:14]=[C:15]([N:18]3[CH2:19][CH2:20][CH:21]([C:24]4[CH:29]=[CH:28][C:2]([O:1][CH2:5][CH2:4][OH:3])=[CH:26][CH:25]=4)[CH2:22][CH2:23]3)[CH2:16][CH2:17][C:12]2=[N:11][N:10]=1

Participants

5

Reactant 3

HCID 7303Ethylene carbonateHCID 11430Potassium CarbonateHCID 685004304-{1-[3-(Trifluoromethyl)-7,8-dihydro[1,2,4]triazolo[4,3-b]pyridazin-6-yl]piperidin-4-yl}phenol

Product 1

HCID 685003122-(4-{1-[3-(Trifluoromethyl)-7,8-dihydro[1,2,4]triazolo[4,3-b]pyridazin-6-yl]piperidin-4-yl}phenoxy)ethanolYield 68.5%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Conditions

Temperature
80 °C

Procedure

1,3-Dioxolan-2-one (1093 mg, 12.41 mmol) was added to 4-{1-[3-(trifluoromethyl)-7,8-dihydro[1,2,4]triazolo[4,3-b]pyridazin-6-yl]piperidin-4-yl}phenol (907 mg, 2.48 mmol) and potassium carbonate (686 mg, 4.97 mmol) in DMF (10 mL). The resulting mixture was stirred at 80° C. for 16 hours. The reaction mixture was evaporated to dryness, the residue redissolved in DCM (100 mL) and the solution washed with water (100 mL). The aqueous washings were re-extracted with DCM (100 mL), then the combined organic phases were washed with saturated brine (50 mL), dried over MgSO4, filtered and evaporated to afford crude product. The crude product was purified by flash silica chromatography, elution gradient 0 to 2% MeOH in EtOAc. Pure fractions were evaporated to dryness to afford 2-(4-{1-[3-(trifluoromethyl)-7,8-dihydro[1,2,4]triazolo[4,3-b]pyridazin-6-yl]piperidin-4-yl}phenoxy)ethanol (695 mg, 68%).

Workup

  1. customThe reaction mixture was evaporated to dryness
  2. dissolutionthe residue redissolved in DCM (100 mL)
  3. washthe solution washed with water (100 mL)
  4. extractionThe aqueous washings were re-extracted with DCM (100 mL)
  5. washthe combined organic phases were washed with saturated brine (50 mL)
  6. dry with materialdried over MgSO4
  7. filtrationfiltered
  8. customevaporated
  9. customto afford crude product
  10. customThe crude product was purified by flash silica chromatography, elution gradient 0 to 2% MeOH in EtOAc
  11. customPure fractions were evaporated to dryness

Sources & evidence

ORD record
ord-51a729008d8b43c9b12ffe5339e62d39
Source dataset
uspto-grants-2012_09
Patent number
US08258140B2

Reaction notes

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