Sodium Hydroxide → 4-Chloro-6-iodo-3-phenyl-2-(trifluoromethyl)quinoline

Reaction equation

[I:1][C:2]1[CH:3]=[C:4]2[C:9](=[CH:10][CH:11]=1)[N:8]=[C:7]([C:12]([F:15])([F:14])[F:13])[C:6]([C:16]1[CH:21]=[CH:20][CH:19]=[CH:18][CH:17]=1)=[C:5]2O.P(Cl)(Cl)([Cl:25])=O.[OH-].[Na+].[NH4+].[OH-]>>[Cl:25][C:5]1[C:4]2[C:9](=[CH:10][CH:11]=[C:2]([I:1])[CH:3]=2)[N:8]=[C:7]([C:12]([F:15])([F:14])[F:13])[C:6]=1[C:16]1[CH:21]=[CH:20][CH:19]=[CH:18][CH:17]=1

Participants

Reactant 4

HCID 14798Sodium Hydroxide

HCID 14923Ammonium Hydroxide

HCID 24813Phosphorus oxychloride

HCID 178515324HCID 178515324, compound

Product 1

HCID 867160644-Chloro-6-iodo-3-phenyl-2-(trifluoromethyl)quinoline

Procedure

A solution of 6-iodo-3-phenyl-2-(trifluoromethyl)quinolin-4-ol (1.54 g, 3.71 mmol, Intermediate 5, step a) in phosphoryl trichloride (5 mL, 53.8 mmol) was heated at 110° C. for 1 hour 45 min, and then cooled to room temperature. Ice-water was added, and the mixture was basified at 4° C. with 50% NaOH and conc. NH4OH until pH 9. The precipitated solid was filtered, washed with water and Et2O, and dried to provide the title compound. The filtrate was separated and the aqueous layer was extracted with CH2Cl2. The combined organic phases were dried (Na2SO4), filtered, concentrated, and purified by flash column chromatography (80 g silica gel column, 0-5% EtOAc in heptane), affording a mixture of the title compound and des-iodo by-product in about 8:1 ratio as a thick oil, which solidified overnight.