Dimethylformamide → (6-Bromopyridin-2-yl)methanol

HRID 2267020Notes

Reaction equation

HRID 2267020 reaction equation
C([Li])CCC.Br[C:7]1[CH:12]=[CH:11][CH:10]=[C:9]([Br:13])[N:8]=1.CN(C)[CH:16]=[O:17].[BH4-].[Na+]>O1CCCC1.C(O)C>[Br:13][C:9]1[N:8]=[C:7]([CH2:16][OH:17])[CH:12]=[CH:11][CH:10]=1

Participants

7

Reactant 4

HCID 6228DimethylformamideHCID 122742,6-DibromopyridineHCID 4311764Sodium borohydrideHCID 178418339Butyllithium

Product 1

HCID 3517811(6-Bromopyridin-2-yl)methanolYield 42.9%

Reagents, catalysts & solvents 2

HCID 702EthanolSolventHCID 8028TetrahydrofuranSolvent

Procedure

Add n-butyl lithium (16.2 mL, 2.5 M in hexanes, 40.5 mmol) dropwise to a solution of 2,6-dibromopyridine (8.00 g, 33.8 mmol) in tetrahydrofuran (100 mL) at −78° C. Stir 30 minutes then add dimethylformamide (12.3 g, 169 mmol) via syringe. Allow solution to warm to ambient temperature then pour it into a solution of sodium borohydride (17.85 g, 338 mmol) in ethanol (50 mL) at −10° C. After 10 minutes, remove the cooling bath. After 1 hour at ambient temperature, add water and 1N hydrochloric acid (gas evolution), then add saturated sodium bicarbonate solution until the mixture is neutralized. Extract the aqueous phase with ethyl acetate, dry over sodium sulfate, filter and concentrate under reduced pressure. Dissolve the residue in diethyl ether and add an excess of hydrogen chloride (2N in diethyl ether). Decant the organic phase and add saturated sodium bicarbonate solution to the residue. Extract with ethyl acetate (3×), dry over sodium sulfate, filter and concentrate under reduced pressure to afford the title compound as a brown oil (2.73 g, 14.5 mmol): MS (m/z): 189 (M+1).

Workup

  1. waitAfter 10 minutes
  2. customremove the cooling bath
  3. waitAfter 1 hour at ambient temperature
  4. additionadd water and 1N hydrochloric acid (gas evolution)
  5. extractionExtract the aqueous phase with ethyl acetate
  6. dry with materialdry over sodium sulfate
  7. filtrationfilter
  8. concentrationconcentrate under reduced pressure
  9. dissolutionDissolve the residue in diethyl ether
  10. additionadd an excess of hydrogen chloride (2N in diethyl ether)
  11. customDecant the organic phase
  12. additionadd saturated sodium bicarbonate solution to the residue
  13. extractionExtract with ethyl acetate (3×)
  14. dry with materialdry over sodium sulfate
  15. filtrationfilter
  16. concentrationconcentrate under reduced pressure

Sources & evidence

ORD record
ord-0f250a9619bd439a9c53a1f56ed9b2d9
Source dataset
uspto-grants-2010_12
Patent number
US07858646B2

Reaction notes

Loading…