Reaction #50933

Reaction equation

NaHSO4

2-Chloro-6-(hydroxymethyl)-3-pyridinol

NaHCO3

iodine

→

2-chloro-6-(hydroxymethyl)-4-iodo-3-pyridinol

Yield 62.0%

Solvents

water

Conditions

Workup

1. 1
   Otheris placed in an ice bath
2. 2
   workup.STIRRINGthe reaction is stirred over the weekend at rt
3. 3
   Extractionthe mixture is extracted with 4×50 mL EtOAc
4. 4
   DryingThe combined organic layer is dried over anhydrous MgSO4
5. 5
   Filtrationis filtered
6. 6
   Concentrationthe filtrate is concentrated in vacuo to a yellow solid
7. 7
   WashThe crude solid is washed with EtOAc

Procedure

2-Chloro-6-(hydroxymethyl)-3-pyridinol (11.6 g, 72.7 mmol) and NaHCO3 (18.3 g, 218 mmol) are added to 200 mL water. The mixture is stirred until homogeneous, the flask is placed in an ice bath, iodine (19.4 g, 76.3 mmol) is added, and the reaction is stirred over the weekend at rt. The pH of the mixture is adjusted to 3 with 2N NaHSO4, and the mixture is extracted with 4×50 mL EtOAc. The combined organic layer is dried over anhydrous MgSO4, is filtered, and the filtrate is concentrated in vacuo to a yellow solid. The crude solid is washed with EtOAc to provide 2-chloro-6-(hydroxymethyl)-4-iodo-3-pyridinol as an off-white solid (62% yield), and the filtrate is concentrated to a small volume and is chromatographed over 250 g silica gel (230-400 mesh) eluting with 2.5:4.5:4:0.1 EtOAc/CH2Cl2/hexane/acetic acid. The desiredd fractionawere combined and concentrated to afford additional pure (12% yield). MS (EI) for C6H5ClINO2, m/z: 285(M)+.

Source