Iodine → Methyl 5-hydroxy-6-iodopyridine-3-carboxylate

HRID 1949847Notes

Reaction equation

HRID 1949847 reaction equation
[CH3:1][O:2][C:3](=[O:11])[C:4]1[CH:9]=[C:8]([OH:10])[CH:7]=[N:6][CH:5]=1.O1CCCC1.O.C(=O)([O-])[O-].[Na+].[Na+].[I:24]I>>[OH:10][C:8]1[C:7]([I:24])=[N:6][CH:5]=[C:4]([CH:9]=1)[C:3]([O:2][CH3:1])=[O:11]

Participants

6

Reactant 5

HCID 807IodineHCID 962WaterHCID 8028TetrahydrofuranHCID 10340Sodium CarbonateHCID 354317Methyl 5-hydroxypyridine-3-carboxylate

Product 1

HCID 57900098Methyl 5-hydroxy-6-iodopyridine-3-carboxylateYield 81.2%

Procedure

To solution of 5-hydroxy-nicotinic acid methyl ester (2.50 g, 16.3 mmol) in tetrahydrofuran (50.0 mL, 616 mmol)/water (50.0 mL, 2780 mmol) was added sodium carbonate (5.19 g, 49.0 mmol) and iodine (10.4 g, 40.8 mmol). The reaction mixture was stirred at room temperature 4 h. The aqueous layer containing product was separated and wash with hexane. The organic layer was neutralized to pH 7 with HCl, extracted EtOAc 4×. The combined organic layers was dried Na2SO4, concentrated. The crude product was purified by flash chromatography (EtOAc/DCM) (eluted at 40 EtOAc) to give methyl 5-hydroxy-6-iodonicotinate (81.2%). MS: (ESI+) 280.0

Workup

  1. additionThe aqueous layer containing product
  2. customwas separated
  3. washwash with hexane
  4. extractionextracted EtOAc 4×
  5. concentrationconcentrated
  6. customThe crude product was purified by flash chromatography (EtOAc/DCM) (eluted at 40 EtOAc)

Sources & evidence

ORD record
ord-0c3b42a43657431292d180b39457ddfc
Source dataset
uspto-grants-2013_03
Patent number
US08399690B2

Reaction notes

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