Sodium hydride → HCID 67340712, compound

HRID 1675070Notes

Reaction equation

HRID 1675070 reaction equation
[H-].[Na+].[O:3]1[CH2:8][CH2:7][CH2:6][CH2:5][CH:4]1[CH:9]([OH:12])CO.O1CCC(OCC2CC[N:24]([C:27]3[CH:28]=[CH:29][C:30]4[N:31]([C:33]([C:36]([F:39])([F:38])[F:37])=[N:34][N:35]=4)[N:32]=3)[CH2:23][CH2:22]2)CC1.O.C1(C)C=CC(S(O)(=O)=O)=CC=1>>[F:38][C:36]([F:37])([F:39])[C:33]1[N:31]2[N:32]=[C:27]([N:24]3[CH2:5][CH2:6][CH:7]([CH2:8][O:3][CH2:4][CH2:9][OH:12])[CH2:22][CH2:23]3)[CH:28]=[CH:29][C:30]2=[N:35][N:34]=1

Participants

5

Reactant 4

HCID 24758Sodium hydrideHCID 521998p-Toluenesulfonic acid monohydrateHCID 19424577HCID 19424577, compoundHCID 59149778HCID 59149778, compound

Product 1

HCID 67340712HCID 67340712, compoundYield 54.3%

Conditions

Temperature
100 °C

Procedure

Sodium hydride (60% dispersion in oil, 0.180 g, 4.5 mmol) was added to neat tetrahydropyranylethyleneglycol (3 g, 20.5 mmol). When the effervescence had subsided 6-[4-(methanesulfonyloxymethyl)piperidin-1-yl]-3-(trifluoromethyl)-[1,2,4]triazolo[4,3-b]pyridazine (obtained as described in Example 294, preparation of starting materials) (1.138 g, 3 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 crude intermediate was disolved in methanol (20 mL) and p-toluenesulfonic acid monohydrate (0.855 g, 4.5 mmol) was added. The solution was stirred for 1 hour and then evaporated. The reaction mixture was partitioned between DCM and water and the organic phase was washed with water and brine, dried over MgSO4 and evaporated. The product was isolated by MPLC silica chromatography, eluting with 5% methanol/DCM. The product containing fractions were evaporated giving a crystalline solid which was triturated with ether, giving 2-[[1-[3-(trifluoromethyl)[1,2,4]triazolo[4,3-b]pyridazin-6-yl]piperidin-4-yl]methoxy]ethanol (0.563 g, 54%)

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. customevaporated
  7. customThe reaction mixture was partitioned between DCM and water
  8. washthe organic phase was washed with water and brine
  9. dry with materialdried over MgSO4
  10. customevaporated
  11. customThe product was isolated by MPLC silica chromatography
  12. washeluting with 5% methanol/DCM
  13. additionThe product containing fractions
  14. customwere evaporated
  15. customgiving a crystalline solid which
  16. customwas triturated with ether

Sources & evidence

ORD record
ord-b502037292e94bf9b91a703bdbe0d890
Source dataset
uspto-grants-2011_08
Patent number
US08003649B2

Reaction notes

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