Chloropyrazine → 1,4-Dioxaspiro[4.5]decan-8-ol, 8-[5-(2-pyrazinyl)-2-pyridinyl]-

HRID 1173276Notes

Reaction equation

HRID 1173276 reaction equation
Br[C:2]1[CH:3]=[CH:4][C:5]([C:8]2([OH:18])[CH2:17][CH2:16][C:11]3([O:15][CH2:14][CH2:13][O:12]3)[CH2:10][CH2:9]2)=[N:6][CH:7]=1.C([Mg]Cl)(C)C.C1(P(C2C=CC=CC=2)CCP(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.Cl[C:53]1[CH:58]=[N:57][CH:56]=[CH:55][N:54]=1>C1COCC1.C/C(/[O-])=C/C(C)=O.C/C(/[O-])=C/C(C)=O.[Ni+2]>[N:54]1[CH:55]=[CH:56][N:57]=[CH:58][C:53]=1[C:2]1[CH:3]=[CH:4][C:5]([C:8]2([OH:18])[CH2:17][CH2:16][C:11]3([O:15][CH2:14][CH2:13][O:12]3)[CH2:10][CH2:9]2)=[N:6][CH:7]=1

Participants

7

Reactant 4

HCID 73277ChloropyrazineHCID 742671,2-Bis(diphenylphosphino)ethaneHCID 57803252HCID 57803252, compoundHCID 178418918HCID 178418918, compound

Product 1

HCID 595561541,4-Dioxaspiro[4.5]decan-8-ol, 8-[5-(2-pyrazinyl)-2-pyridinyl]-Yield 19.1%

Reagents, catalysts & solvents 2

HCID 9834912Nickel(II) acetylacetonateCatalystHCID 8028TetrahydrofuranSolvent2×

Procedure

To a solution of 8-(5-bromopyridin-2-yl)-1,4-dioxaspiro[4.5]decan-8-ol (0.50 g, 1.59 mmol) in THF (7.5 mL) was dropwise added isopropyl magnesium chloride (2 M in THF, 1.8 mL) at rt. After stirred for 1 hour, the solution was degassed with N2 three times. To another degassed solution of THF (2.5 mL) at rt was added nickel acetylacetonate (20 mg, 0.080 mmol) and 1,2-bis(diphenylphosphino)-ethane (32 mg, 0.080 mmol) under N2 flush. After stirred for 10 mins, 2-chloropyrazine (0.155 mL, 1.59 mmol) was added in, and the resulting mixture was stirred for 30 minutes. The mixture was then transferred to a freshly prepared solution of the Grignard reagent prepared previously. The mixture was stirred at rt for 18 hours, and was quenched with saturated NH4Cl solution. The aqueous solution was extracted with ethyl acetate, and the combined organic phase was washed with saline solution (2×50 mL), dried over MgSO4, concentrated in vacuo. The residue was chromatographed on SiO2, eluted with hexane/ethyl acetate (1 to 1), and the appropriate fractions were collected to provide 8-(5-pyrazin-2-ylpyridin-2-yl)-1,4-dioxaspiro[4.5]decan-8-ol (95 mg, 19%) as an oil. LCMS: 314.2 (M+H+, 100%).

Workup

  1. customat rt
  2. customthe solution was degassed with N2 three times
  3. customflush
  4. stirringAfter stirred for 10 mins
  5. stirringwas stirred for 30 minutes
  6. customprepared previously
  7. stirringThe mixture was stirred at rt for 18 hours
  8. customwas quenched with saturated NH4Cl solution
  9. extractionThe aqueous solution was extracted with ethyl acetate
  10. washthe combined organic phase was washed with saline solution (2×50 mL)
  11. dry with materialdried over MgSO4
  12. concentrationconcentrated in vacuo
  13. customThe residue was chromatographed on SiO2
  14. washeluted with hexane/ethyl acetate (1 to 1)
  15. customthe appropriate fractions were collected

Sources & evidence

ORD record
ord-738b9e0d27ab427296fbca77bf53da72
Source dataset
uspto-grants-2010_11
Patent number
US07834021B2

Reaction notes

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