Sodium hydride → HCID 67341254, compound

HRID 1675068Notes

Reaction equation

HRID 1675068 reaction equation
[H-].[Na+].[C:3]([O:7][CH3:8])(=[O:6])[CH2:4][OH:5].CS(O[CH2:14][CH:15]1[CH2:20][CH2:19][N:18]([C:21]2[CH:22]=[CH:23][C:24]3[N:25]([C:27]([C:30]([F:33])([F:32])[F:31])=[N:28][N:29]=3)[N:26]=2)[CH2:17][CH2:16]1)(=O)=O>>[F:33][C:30]([F:31])([F:32])[C:27]1[N:25]2[N:26]=[C:21]([N:18]3[CH2:17][CH2:16][CH:15]([CH2:14][O:5][CH2:4][C:3]([O:7][CH3:8])=[O:6])[CH2:20][CH2:19]3)[CH:22]=[CH:23][C:24]2=[N:29][N:28]=1

Participants

4

Reactant 3

HCID 24758Sodium hydrideHCID 66774Methyl GlycolateHCID 86638076HCID 86638076, compound

Product 1

HCID 67341254HCID 67341254, compoundYield 17.4%

Conditions

Temperature
100 °C

Procedure

Sodium hydride (60% dispersion in oil, 0.120 g, 3.0 mmol) was added to neat methyl glycolate (1.544 mL, 20.0 mmol). When the effervescence had subsided 6-[4-(methanesulfonyloxymethyl)piperidin-1-yl]-3-(trifluoromethyl)-[1,2,4]triazolo[4,3-b]pyridazine (0.759 g, 2.0 mmol) was added and the mixture was heated at 100° C. for 40 minutes. The reaction mixture was partitioned between DCM and water. The organic phase was washed with water and brine, dried over MgSO4 and evaporated. The product was isolated by MPLC silica chromatography, eluting with ethyl acetate. The product containing fractions were evaporated to an oil which crystallised from ether, giving methyl 2-[[1-[3-(trifluoromethyl)-[1,2,4]triazolo[4,3-b]pyridazin-6-yl]piperidin-4-yl]methoxy]acetate (0.130 g, 17%).

Workup

  1. additionwas added
  2. customThe reaction mixture was partitioned between DCM and water
  3. washThe organic phase was washed with water and brine
  4. dry with materialdried over MgSO4
  5. customevaporated
  6. customThe product was isolated by MPLC silica chromatography
  7. washeluting with ethyl acetate
  8. additionThe product containing fractions
  9. customwere evaporated to an oil which
  10. customcrystallised from ether

Sources & evidence

ORD record
ord-72ce27f724bb4c43851e3a463d05ce67
Source dataset
uspto-grants-2011_08
Patent number
US08003649B2

Reaction notes

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