2-Fluoro-3-(1,4-dioxaspiro[4.5]decan-8-YL)pyrazine → 4-(3-Fluoropyrazin-2-yl)cyclohexanone

HRID 454900Notes

Reaction equation

HRID 454900 reaction equation
[F:1][C:2]1[C:7]([CH:8]2[CH2:17][CH2:16][C:11]3(OCC[O:12]3)[CH2:10][CH2:9]2)=[N:6][CH:5]=[CH:4][N:3]=1>Cl.CC(C)=O>[F:1][C:2]1[C:7]([CH:8]2[CH2:9][CH2:10][C:11](=[O:12])[CH2:16][CH2:17]2)=[N:6][CH:5]=[CH:4][N:3]=1

Participants

4

Reactant 1

HCID 585479812-Fluoro-3-(1,4-dioxaspiro[4.5]decan-8-YL)pyrazine

Product 1

HCID 585477714-(3-Fluoropyrazin-2-yl)cyclohexanoneYield 70.1%

Reagents, catalysts & solvents 2

HCID 180AcetoneSolvent2×HCID 313Hydrochloric AcidSolvent

Procedure

A solution of 2-fluoro-3-(1,4-dioxaspiro[4.5]decan-8-yl)pyrazine (91 g, 0.382 mol, 1.0 eq.) in 1N aqueous HCl (573 mL) and acetone (4 L) was heated to 37° C. overnight. The reaction mixture was cooled to room temperature and most of acetone was removed under reduced pressure. The crude material was diluted with EtOAc (4 L) and the solution was washed with aqueous saturated NaHCO3 (500 mL×2), water (500 mL), brine (500 mL), dried over Na2SO4, filtered, and evaporated. The crude product was purified by column chromatography (100% hexanes to 50% EtOAc in hexanes, Rf=0.3 in 30% EtOAc in hexanes) to give 52 g (70% yield) of 4-(3-fluoropyrazin-2-yl)cyclohexanone. GC-MS: 195 (M+1); calcd for C10H11FN2O: 194.21

Workup

  1. customwas removed under reduced pressure
  2. additionThe crude material was diluted with EtOAc (4 L)
  3. washthe solution was washed with aqueous saturated NaHCO3 (500 mL×2), water (500 mL), brine (500 mL)
  4. dry with materialdried over Na2SO4
  5. filtrationfiltered
  6. customevaporated
  7. customThe crude product was purified by column chromatography (100% hexanes to 50% EtOAc in hexanes, Rf=0.3 in 30% EtOAc in hexanes)

Sources & evidence

ORD record
ord-9fd34bc2fff14cdfae81c288b7f37daf
Source dataset
uspto-grants-2013_07
Patent number
US08497265B2

Reaction notes

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