3,5-Dibromopyridine → 4-(5-Bromo-3-pyridinyl)tetrahydro-2H-pyran-4-ol

HRID 712659Notes

Reaction equation

HRID 712659 reaction equation
Br[C:2]1[CH:3]=[N:4][CH:5]=[C:6]([Br:8])[CH:7]=1.[O:9]1[CH2:14][CH2:13][C:12](=[O:15])[CH2:11][CH2:10]1>C1COCC1>[Br:8][C:6]1[CH:7]=[C:2]([C:12]2([OH:15])[CH2:13][CH2:14][O:9][CH2:10][CH2:11]2)[CH:3]=[N:4][CH:5]=1

Participants

4

Reactant 2

HCID 693693,5-DibromopyridineHCID 121599Tetrahydro-4H-pyran-4-one

Product 1

HCID 1176670474-(5-Bromo-3-pyridinyl)tetrahydro-2H-pyran-4-olYield 26%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Conditions

Temperature
-10 °C

Procedure

To 3,5-dibromopyridine (592 mg, 2.50 mmol) in 2 mL of THF at −20° C. is added 1.3M i-PrMgCl_LiCl solution (1.83 mL, 2.4 mmol) in one portion. The mixture is allowed to stir for 30 min., warming to −10° C. The mixture is cooled to −20° C. and tetrahydro-pyran-4-one (0.23 mL, 3.00 mmol) is added. The reaction is quenched with 50 mL of saturated aqueous NH4Cl and diluted with 200 mL EtOAc. The organic phase is washed with 2×100 mL of H2O, 1×100 mL of brine. The organic phase is dried with MgSO4, filtered and concentrated. The crude material is applied to a silica column and purified (0-10% MeOH/CH2Cl2) to give 168 mg of 4-(5-bromo-pyridin-3-yl)-tetrahydro-pyran-4-ol.

Workup

  1. temperatureThe mixture is cooled to −20° C.
  2. customThe reaction is quenched with 50 mL of saturated aqueous NH4Cl
  3. additiondiluted with 200 mL EtOAc
  4. washThe organic phase is washed with 2×100 mL of H2O, 1×100 mL of brine
  5. dry with materialThe organic phase is dried with MgSO4
  6. filtrationfiltered
  7. concentrationconcentrated
  8. custompurified (0-10% MeOH/CH2Cl2)

Sources & evidence

ORD record
ord-f456b4d2351b4cc2addf091448bf8d3c
Source dataset
uspto-grants-2015_11
Patent number
US09181272B2

Reaction notes

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