5-bromo-2,4-dichloropyridine → HCID 90204301, compound

HRID 1480186Notes

Reaction equation

HRID 1480186 reaction equation
Br[C:2]1[C:3]([Cl:9])=[CH:4][C:5]([Cl:8])=[N:6][CH:7]=1.C([Mg]Cl)(C)C.[O:15]1[CH2:18][C:17](=[O:19])[CH2:16]1>C1COCC1.C(OCC)(=O)C>[Cl:9][C:3]1[CH:4]=[C:5]([Cl:8])[N:6]=[CH:7][C:2]=1[C:17]1([OH:19])[CH2:18][O:15][CH2:16]1

Participants

6

Reactant 3

HCID 121751335-bromo-2,4-dichloropyridineHCID 150242543-OxetanoneHCID 178418918HCID 178418918, compound

Product 1

HCID 90204301HCID 90204301, compoundYield 72%

Reagents, catalysts & solvents 2

HCID 8028TetrahydrofuranSolventHCID 8857Ethyl AcetateSolvent

Conditions

Temperature
-15 °C

Procedure

To a solution of 5-bromo-2,4-dichloropyridine (CAN 849937-96-8, 15 g, 66.1 mmol) in dry THF (300 ml) cooled down to −15° C. under an argon atmosphere was added isopropyl magnesium chloride, lithium chloride complex (53.4 ml, 69.4 mmol) and the mixture was stirred at −15° C. for 1 hour. Then oxetan-3-one (5.24 g, 72.7 mmol) was added neat to the reaction mixture cooled at −15° C., reaction mixture was stirred and let to warm up to room temperature overnight. Reaction was quenched by addition of water and stirred for 5 minutes. Reaction was diluted with ethyl acetate and was transferred into a separatory funnel. The organic phase was extracted with a saturated aqueous solution of ammonium chloride and the organic phase was collected. The aqueous phase was back-extracted with ethyl acetate. The combined organic phases were dried over sodium sulfate and evaporated down to dryness. The crude material was purified by flash chromatography on silica eluting with a heptane/ethyl acetate gradient to yield the title compound (10.5 mg, 72%). MS (ESI, m/z): 220.4 (M+H+)

Workup

  1. temperaturecooled at −15° C.
  2. customreaction mixture
  3. stirringwas stirred
  4. temperatureto warm up to room temperature overnight
  5. customReaction
  6. customwas quenched by addition of water
  7. stirringstirred for 5 minutes
  8. customReaction
  9. customwas transferred into a separatory funnel
  10. extractionThe organic phase was extracted with a saturated aqueous solution of ammonium chloride
  11. customthe organic phase was collected
  12. extractionThe aqueous phase was back-extracted with ethyl acetate
  13. dry with materialThe combined organic phases were dried over sodium sulfate
  14. customevaporated down to dryness
  15. customThe crude material was purified by flash chromatography on silica eluting with a heptane/ethyl acetate gradient

Sources & evidence

ORD record
ord-d112e010cb6e4d47b6544c84d4c6668f
Source dataset
uspto-grants-2016_08
Patent number
US09409866B2

Reaction notes

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