Ammonium formate → Ethyl 2-[4-[1-[3-(trifluoromethyl)-7,8-dihydro-[1,2,4]triazolo[4,3-b]pyridazin-6-yl]piperidin-4-yl]phenoxy]acetate

HRID 2381116Notes

Reaction equation

HRID 2381116 reaction equation
[F:1][C:2]([F:31])([F:30])[C:3]1[N:7]2[N:8]=[C:9]([N:12]3[CH2:17][CH2:16][CH:15]([C:18]4[CH:29]=[CH:28][C:21]([O:22][CH2:23][C:24]([O:26][CH3:27])=[O:25])=[CH:20][CH:19]=4)[CH2:14][CH2:13]3)[CH:10]=[CH:11][C:6]2=[N:5][N:4]=1.[CH:32]([O-])=O.[NH4+]>[Pd].C(O)C>[F:31][C:2]([F:1])([F:30])[C:3]1[N:7]2[N:8]=[C:9]([N:12]3[CH2:17][CH2:16][CH:15]([C:18]4[CH:29]=[CH:28][C:21]([O:22][CH2:23][C:24]([O:26][CH2:27][CH3:32])=[O:25])=[CH:20][CH:19]=4)[CH2:14][CH2:13]3)[CH2:10][CH2:11][C:6]2=[N:5][N:4]=1

Participants

5

Reactant 2

HCID 2723923Ammonium formate2×HCID 67342348Methyl 2-[4-[1-[3-(trifluoromethyl)-[1,2,4]triazolo[4,3-b]pyridazin-6-yl]piperidin-4-yl]phenoxy]acetate

Product 1

HCID 68503106Ethyl 2-[4-[1-[3-(trifluoromethyl)-7,8-dihydro-[1,2,4]triazolo[4,3-b]pyridazin-6-yl]piperidin-4-yl]phenoxy]acetateYield 72.2%

Reagents, catalysts & solvents 2

HCID 23938PalladiumCatalystHCID 702EthanolSolvent

Procedure

10% Palladium on carbon (0.536 g, 0.50 mmol) was added to methyl 2-[4-[1-[3-(trifluoromethyl)-[1,2,4]triazolo[4,3-b]pyridazin-6-yl]piperidin-4-yl]phenoxy]acetate (1.096 g, 2.52 mmol) and ammonium formate (1.587 g, 25.17 mmol) in ethanol (50 mL). The resulting mixture was stirred at 78° C., with further portions of ammonium formate being added every 5 hours until the reaction was complete. The reaction mixture was cooled to room temperature and the catalyst was removed by filtration. The filtrate was evaporated to dryness, redissolved in DCM (100 mL) and the solution was washed with water (50 mL) followed by brine (50 mL), then the solvents were evaporated to give crude product. The crude product was purified by flash silica chromatography, eluting with a gradient of 50 to 80% EtOAc in isohexane. Pure fractions were evaporated to afford ethyl 2-[4-[1-[3-(trifluoromethyl)-7,8-dihydro-[1,2,4]triazolo[4,3-b]pyridazin-6-yl]piperidin-4-yl]phenoxy]acetate (0.820 g, 72.2%) as a gum.

Workup

  1. additionadded every 5 hours until the reaction
  2. customthe catalyst was removed by filtration
  3. customThe filtrate was evaporated to dryness
  4. dissolutionredissolved in DCM (100 mL)
  5. washthe solution was washed with water (50 mL)
  6. customthe solvents were evaporated
  7. customto give crude product
  8. customThe crude product was purified by flash silica chromatography
  9. washeluting with a gradient of 50 to 80% EtOAc in isohexane
  10. customPure fractions were evaporated

Sources & evidence

ORD record
ord-db9a4031de0b4fccb73dd55d8cce5bd7
Source dataset
uspto-grants-2012_09
Patent number
US08258140B2

Reaction notes

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