2-Bromopyridine → HCID 10583661, compound

HRID 2207546Notes

Reaction equation

HRID 2207546 reaction equation
Br[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][N:3]=1.C([Li])CCC.[O:13]1[CH2:18][CH2:17][C:16](=[O:19])[CH2:15][CH2:14]1>C1COCC1>[OH:19][C:16]1([C:2]2[CH:7]=[CH:6][CH:5]=[CH:4][N:3]=2)[CH2:17][CH2:18][O:13][CH2:14][CH2:15]1

Participants

5

Reactant 3

HCID 79732-BromopyridineHCID 121599Tetrahydro-4H-pyran-4-oneHCID 178418339Butyllithium

Product 1

HCID 10583661HCID 10583661, compoundYield 61.2%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Conditions

Temperature
-78 °C

Procedure

To a stirred, cooled solution of 2-bromopyridine (5 g, 31.65 mmol) in THF (75 mL) at −78° C. was added n-butyl lithium (2.5 M in hexanes, 12.66 mL, 31.65 mmol) dropwise and the solution stirred at −78° C. for 10 minutes. After this time, tetrahydro-4H-pyran-4-one (3.49 g, 34.81 mmol) was added, the reaction warmed to ambient temperature and stirred overnight. The reaction was then quenched with saturated aqueous ammonium chloride solution and the THF removed in vacuo. The resultant aqueous phase was twice extracted with ethyl acetate and the combined organic phases dried (magnesium sulfate) and filtered. After concentration in vacuo, purification by column chromatography (SiO2, eluting with 2:1 hexanes:ethyl acetate) gave a residue which was triturated from hexane to yield the title compound (3.47 g, 61%) as a white solid; NMR δH (400 MHz, CDCl3) 8.49 (1H, m), 7.81 (1H, td, J 7.8 Hz, 1.8 Hz), 7.68 (1H, m), 7.25 (1H, ddd, J 7.5 Hz, 4.9 Hz, 1.1 Hz), 3.85 (4H, m), 3.30 (1H, m), 2.30 (2H, td, J 13.3 Hz, 5.3 Hz), 1.54 (1H, dd, J 13.8 Hz, 1.9 Hz); LC-MS Retention time 0.51 min, (M+H)+ 180.

Workup

  1. temperaturethe reaction warmed to ambient temperature
  2. stirringstirred overnight
  3. customThe reaction was then quenched with saturated aqueous ammonium chloride solution
  4. customthe THF removed in vacuo
  5. extractionThe resultant aqueous phase was twice extracted with ethyl acetate
  6. dry with materialthe combined organic phases dried (magnesium sulfate)
  7. filtrationfiltered
  8. concentrationAfter concentration
  9. customin vacuo, purification
  10. washby column chromatography (SiO2, eluting with 2:1 hexanes:ethyl acetate)
  11. customgave a residue which
  12. customwas triturated from hexane

Sources & evidence

ORD record
ord-c5871110e1724637b81e5612a60db0d6
Source dataset
uspto-grants-2016_06
Patent number
US09376443B2

Reaction notes

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