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

HRID 1891678Notes

Reaction equation

HRID 1891678 reaction equation
Br[C:2]1[CH:7]=[CH:6][C:5]([Cl:8])=[CH:4][N:3]=1.CCCCCC.C([Li])CCC.CN(C)[CH:22]=[O:23].[BH4-].[Na+]>O1CCCC1.O.C1(C)C=CC=CC=1>[Cl:8][C:5]1[CH:6]=[CH:7][C:2]([CH2:22][OH:23])=[N:3][CH:4]=1

Participants

8

Reactant 4

HCID 6228DimethylformamideHCID 8170982-Bromo-5-chloropyridineHCID 4311764Sodium borohydrideHCID 178418244HCID 178418244, compound

Product 1

HCID 20537893(5-Chloropyridin-2-yl)methanolYield 47.3%

Reagents, catalysts & solvents 3

HCID 962WaterSolventHCID 1140TolueneSolventHCID 8028TetrahydrofuranSolvent

Procedure

To a mixture of 2-bromo-5-chloropyridine (2.0 g, 10.4 mmol) and toluene (50 ml) was added a 1.6 M n-butyl lithium hexane solution (7.8 mL, 12.5 mmol) at −78° C., which was stirred for 1 hour. N,N-dimethylformamide (4.0 mL, 52.0 mmol) was then added dropwise into the mixture at the same temperature, which was then stirred for a further 15 minutes at room temperature. Water and tetrahydrofuran were added to this reaction solution, followed by vigorous stirring. The organic layer was separated, washed with water and saturated aqueous sodium chloride, dried over anhydrous magnesium sulfate, and filtered. Sodium borohydride (1.18 g, 31.2 mmol) was added at 0° C. to the filtrate, and stirred for 1 hour at room temperature. This reaction solution was partitioned into 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, and the resulting residue was purified by NH silica gel column chromatography (hexane:diethyl ether=1:2) to obtain the title compound (706 mg, 47%).

Workup

  1. stirringwas then stirred for a further 15 minutes at room temperature
  2. customThe organic layer was separated
  3. washwashed with water and saturated aqueous sodium chloride
  4. dry with materialdried over anhydrous magnesium sulfate
  5. filtrationfiltered
  6. stirringstirred for 1 hour at room temperature
  7. customThis reaction solution was partitioned into water and tetrahydrofuran
  8. customThe organic layer was separated
  9. washwashed with saturated aqueous sodium chloride
  10. dry with materialdried over anhydrous magnesium sulfate
  11. filtrationfiltered
  12. concentrationThe filtrate was concentrated under a reduced pressure
  13. customthe resulting residue was purified by NH silica gel column chromatography (hexane:diethyl ether=1:2)

Sources & evidence

ORD record
ord-380c8fe808244bbe81f35770d0e65d0a
Source dataset
uspto-grants-2013_08
Patent number
US08507530B2

Reaction notes

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