Sodium Hydroxide → 3-Iodo-5-methoxy-2-phenyl-pyridin-4-ylamine

HRID 917460Notes

Reaction equation

[CH3:1][O:2][C:3]1[C:4]([NH2:15])=[CH:5][C:6]([C:9]2[CH:14]=[CH:13][CH:12]=[CH:11][CH:10]=2)=[N:7][CH:8]=1.[I:16]([O-])(=O)=O.[K+].[OH-].[Na+]>[Cl-].[Na+].O>[I:16][C:5]1[C:6]([C:9]2[CH:14]=[CH:13][CH:12]=[CH:11][CH:10]=2)=[N:7][CH:8]=[C:3]([O:2][CH3:1])[C:4]=1[NH2:15]

Participants

Conditions

Temperature: 100 °C

Procedure

To an ice-cooled stirred suspension of 2.70 g (6.20 mmol) 5-methoxy-2-phenyl-pyridin-4-ylamine in 3 ml distilled water was added dropwise 3 ml concentrated sulfuric acid and the mixture was then warmed to 100° C. 1.30 g (6.07 mmol) potassium iodate was added after 3 h, a further 1.30 g (6.07 mmol) potassium iodate was added after an additional 3 h, and finally a further 0.75 g (3.50 mmol) potassium iodate was added after an additional 3 h. Stirred was continued for a further 2.5 h at 100° C., and then the mixture was allowed to cool to room temperature on standing overnight. The mixture was then diluted with saturated brine, made basic by addition of 30% aq. sodium hydroxide solution, and extracted three times with tetrahydrofuran. The combined organic phases were dried over sodium sulfate and concentrated in vacuo. Flash chromatography (ethyl acetate/heptane) afforded 1.60 g (79%) 3-iodo-5-methoxy-2-phenyl-pyridin-4-ylamine as an orange oil which crystallized on standing. ES-MS m/e (%): 327 (M+H+, 100).

Workup

distillationdistilled water
additionwas added dropwise 3 ml concentrated sulfuric acid
stirringStirred
temperatureto cool to room temperature
waiton standing overnight
extractionextracted three times with tetrahydrofuran
dry with materialThe combined organic phases were dried over sodium sulfate
concentrationconcentrated in vacuo

Sources & evidence

ORD record: ord-73807b05f7a04c5c879538c83ac05114
Source dataset: uspto-grants-2007_09
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US07273865B2

Reaction notes

Loading…