5-Bromo-2-methoxypyridine → 1,1-Bis(6-methoxypyridin-3-yl)methanamine

HRID 2059744Notes

Reaction equation

HRID 2059744 reaction equation
Br[C:2]1[CH:3]=[CH:4][C:5]([O:8][CH3:9])=[N:6][CH:7]=1.C([Li])CCC.[CH3:15][O:16][C:17]1[N:22]=[CH:21][C:20]([C:23]#[N:24])=[CH:19][CH:18]=1.[BH4-].[Na+]>C1COCC1.CO>[CH3:9][O:8][C:5]1[N:6]=[CH:7][C:2]([CH:23]([C:20]2[CH:21]=[N:22][C:17]([O:16][CH3:15])=[CH:18][CH:19]=2)[NH2:24])=[CH:3][CH:4]=1

Participants

7

Reactant 4

HCID 27348955-Bromo-2-methoxypyridineHCID 27367762-Methoxy-5-pyridinecarbonitrileHCID 4311764Sodium borohydrideHCID 178418339Butyllithium

Product 1

HCID 578784161,1-Bis(6-methoxypyridin-3-yl)methanamine

Reagents, catalysts & solvents 2

HCID 887MethanolSolventHCID 8028TetrahydrofuranSolvent2×

Procedure

To 5-bromo-2-methoxypyridine (1.00 g, 5.32 mmol) in THF (20 mL) at −78° C. was added n-butyllithium (3.13 mL, 7.83 mmol, 2.5 M in hexane). The reaction was aged at −78° C. for about 25 min at which point the cold bath was removed. 6-methoxypyridine-3-carbonitrile (1.00 g, 7.46 mmol) in THF (10 mL) was added and the reaction aged for about 40 min warming to rt at which point the reaction was concentrated. The residue was diluted with MeOH (20 mL) and NaBH4 (0.282 g 7.46 mmol) was added. The reaction aged about 90 min at rt. The reaction was concentrated and diluted with EtOAc and aq HCl (15 mL, 2 M). The aq portion was extracted twice with EtOAc before adding aq NaOH (20 mL, 2M). The aq portion was then extracted three times with EtOAc. The combined organic portion was concentrated and the residue was purified by flash chromatography on silica gel gradient eluted with 0-100% EtOAc/hexane followed by 0-20% MeOH (containing 1.5% triethylamine)/EtOAc affording the title compound. HPLC/MS: 246 (M+1); Rt=1.61 min.

Workup

  1. customthe cold bath was removed
  2. waitthe reaction aged for about 40 min
  3. concentrationwas concentrated
  4. additionwas added
  5. customThe reaction aged about 90 min
  6. customat rt
  7. concentrationThe reaction was concentrated
  8. additiondiluted with EtOAc and aq HCl (15 mL, 2 M)
  9. extractionThe aq portion was extracted twice with EtOAc
  10. additionbefore adding aq NaOH (20 mL, 2M)
  11. extractionThe aq portion was then extracted three times with EtOAc
  12. concentrationThe combined organic portion was concentrated
  13. customthe residue was purified by flash chromatography on silica gel gradient
  14. washeluted with 0-100% EtOAc/hexane

Sources & evidence

ORD record
ord-256fdc633fbf4a3e86a4ee3bf116c95f
Source dataset
uspto-grants-2012_10
Patent number
US08278304B2

Reaction notes

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