Acetic Acid → (4-Amino-6-bromopyridin-2-yl)methanol

HRID 2307270Notes

Reaction equation

HRID 2307270 reaction equation
[Br:1][C:2]1[N:7]=[C:6]([C:8](O)=[O:9])[CH:5]=[C:4]([N+:11]([O-])=O)[CH:3]=1.B.C1COCC1.C(O)(=O)C>C1COCC1.[Fe]>[NH2:11][C:4]1[CH:3]=[C:2]([Br:1])[N:7]=[C:6]([CH2:8][OH:9])[CH:5]=1

Participants

6

Reactant 3

HCID 176Acetic AcidHCID 2723981Borane;tetrahydrofuranHCID 221765006-Bromo-4-nitropicolinic acid

Product 1

HCID 22176486(4-Amino-6-bromopyridin-2-yl)methanolYield 34%

Reagents, catalysts & solvents 2

HCID 23925IronCatalystHCID 8028TetrahydrofuranSolvent

Procedure

A solution of 6-bromo-4-nitro-pyridine-2-carboxylic acid (example 6a) (6.60 g, 29.1 mmol) in THF (150 ml) was treated with borane/THF (87 ml of a 1M solution). The mixture was refluxed for 6 hr, then powdered iron (16.3 g, 291 mmol) was added, followed by acetic acid (150 ml). Reflux was maintained for 6 hr, the mixture was filtered, evaporated and partitioned (AcOEt/NaHCO3-solution). The organic phase was dried (Na2SO4), concentrated and chromatographed (SiO2 with CH2Cl2/MeOH=93/7) to provide 2.0 g (34%) of (4-amino-6-bromo-pyridin-2-yl)-methanol as a white solid material. Mp. 144-145° C. (AcOEt), MS: m/e=202 (M+).

Workup

  1. temperatureThe mixture was refluxed for 6 hr
  2. temperatureReflux
  3. temperaturewas maintained for 6 hr
  4. filtrationthe mixture was filtered
  5. customevaporated
  6. custompartitioned (AcOEt/NaHCO3-solution)
  7. dry with materialThe organic phase was dried (Na2SO4)
  8. concentrationconcentrated
  9. customchromatographed (SiO2 with CH2Cl2/MeOH=93/7)

Sources & evidence

ORD record
ord-d177ac6e5f62496188cd8fe41506179e
Source dataset
uspto-grants-2004_12
Patent number
US06831087B2

Reaction notes

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