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

HRID 2041305Notes

Reaction equation

HRID 2041305 reaction equation
Br[C:2]1[CH:7]=[CH:6][C:5]([Br:8])=[CH:4][N:3]=1.C([Li])CCC.CCCCCC.CN([CH:23]=[O:24])C.[BH4-].[Na+]>C1(C)C=CC=CC=1.CCOC(C)=O.[NH4+].[Cl-]>[OH:24][CH2:23][C:2]1[CH:7]=[CH:6][C:5]([Br:8])=[CH:4][N:3]=1

Participants

9

Reactant 5

HCID 6228DimethylformamideHCID 8058HexaneHCID 693532,5-DibromopyridineHCID 4311764Sodium borohydrideHCID 178418339Butyllithium

Product 1

HCID 5200169(5-Bromopyridin-2-yl)methanolYield 67.1%

Reagents, catalysts & solvents 3

HCID 1140TolueneSolventHCID 8857Ethyl AcetateSolventHCID 25517Ammonium ChlorideSolvent

Conditions

Temperature
-78 °C

Procedure

Dissolve 2,5-dibromopyridine (10 g, 42 mmol) in toluene (500 mL) and cool to −78° C. Add 2.5M n-butyllithium in hexane (20.3 mL, 50.6 mmol) and stir the mixture for 7 h at the same temperature. Add DMF (4.2 mL, 54.87 mmol) and stir for 1 h. Warm the solution to 0° C. and add sodium borohydride (3.2 g, 84.42 mmol). Stir the mixture at ambient temperature for 3 h. Dilute with EtOAc and saturated aqueous NH4Cl. Separate the layers and extract the aqueous layer three times with EtOAc. Dry over anhydrous Na2SO4, filter and concentrate in vacuo. Recrystallization from hexane/EtOAc (9:1) gives the desired intermediate as a white solid (5.3 g, 66%).

Workup

  1. temperatureWarm the solution to 0° C.
  2. stirringStir the mixture at ambient temperature for 3 h
  3. customSeparate the layers
  4. extractionextract the aqueous layer three times with EtOAc
  5. dry with materialDry over anhydrous Na2SO4
  6. filtrationfilter
  7. concentrationconcentrate in vacuo
  8. customRecrystallization from hexane/EtOAc (9:1)

Sources & evidence

ORD record
ord-a7389231c19e4e2cbc02f094b3d68e9e
Source dataset
uspto-grants-2013_11
Patent number
US08580780B2

Reaction notes

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