Dimethylformamide → (5-Fluoropyridin-2-yl)methanol

HRID 77891Notes

Reaction equation

HRID 77891 reaction equation
Br[C:2]1[CH:7]=[CH:6][C:5]([F:8])=[CH:4][N:3]=1.C([Li])CCC.CN(C)[CH:16]=[O:17].[BH4-].[Na+]>C1(C)C=CC=CC=1.O1CCCC1.O>[F:8][C:5]1[CH:6]=[CH:7][C:2]([CH2:16][OH:17])=[N:3][CH:4]=1

Participants

8

Reactant 4

HCID 6228DimethylformamideHCID 27831712-Bromo-5-fluoropyridineHCID 4311764Sodium borohydrideHCID 178418339Butyllithium

Product 1

HCID 24729312(5-Fluoropyridin-2-yl)methanolYield 36%

Reagents, catalysts & solvents 3

HCID 962WaterSolventHCID 1140TolueneSolventHCID 8028TetrahydrofuranSolvent

Procedure

To a solution of 2-bromo-5-fluoropyridine (3.67 g, 20.8 mmol) in toluene (100 mL) was added dropwise n-butyl lithium (15.6 mL, 1.6 M hexane solution, 25.0 mmol) under nitrogen atmosphere at −78° C., which was stirred for 30 minutes. N,N-Dimethylformamide (8.05 mL, 104.0 mmol) was added dropwise to this solution at −78° C., and stirred for 20 minutes at 0° C. This reaction solution was vigorously stirred after addition of water and tetrahydrofuran. The organic layer was separated, washed with water and saturated aqueous sodium chloride, dried over anhydrous magnesium sulfate and filtered. Sodium borohydride (1.58 g, 41.8 mmol) was added to the filtrate at 0° C., and stirred for 1 hour at room temperature. This reaction solution was partitioned by addition of water and tetrahydrofuran. The organic layer was separated, washed with saturated aqueous sodium chloride, dried over anhydrous magnesium sulfate and filtered. The filtrate was concentrated under a reduced pressure. The resulting residue was purified by NH silica gel column chromatography (hexane: diethyl ether=1:2) to obtain the title compound (945 mg, 36%).

Workup

  1. stirringstirred for 20 minutes at 0° C
  2. stirringThis reaction solution was vigorously stirred
  3. customThe organic layer was separated
  4. washwashed with water and saturated aqueous sodium chloride
  5. dry with materialdried over anhydrous magnesium sulfate
  6. filtrationfiltered
  7. stirringstirred for 1 hour at room temperature
  8. customThis reaction solution was partitioned by addition of water and tetrahydrofuran
  9. customThe organic layer was separated
  10. washwashed with saturated aqueous sodium chloride
  11. dry with materialdried over anhydrous magnesium sulfate
  12. filtrationfiltered
  13. concentrationThe filtrate was concentrated under a reduced pressure
  14. customThe resulting residue was purified by NH silica gel column chromatography (hexane: diethyl ether=1:2)

Sources & evidence

ORD record
ord-a302f15c0d654238af51e6f7f9f3e470
Source dataset
uspto-grants-2014_09
Patent number
US08841327B2

Reaction notes

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