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

HRID 1478507Notes

Reaction equation

HRID 1478507 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

5

Reactant 4

HCID 14798Sodium HydroxideHCID 14923Ammonium HydroxideHCID 24813Phosphorus oxychlorideHCID 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 20: step a) in phosphoryl trichloride (5 mL, 53.8 mmol) was heated at 110° C. for 1 hour 45 minutes, and then cooled to room temperature. Ice-water was added, and the mixture was basified at 4° C. with 50% aqueous NaOH and concentrated 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), concentrated, and purified by flash column chromatography (80 g silica gel column, 0-5% EtOAc in heptanes), affording a mixture of the title compound and des-iodo by-product, 4-chloro-3-phenyl-2-(trifluoromethyl)quinoline, in about 8:1 ratio as a thick oil, which solidified over night.

Workup

  1. filtrationThe precipitated solid was filtered
  2. washwashed with water and Et2O
  3. customdried

Sources & evidence

ORD record
ord-c0b065346af148518f68c18bb8078893
Source dataset
uspto-grants-2016_08
Patent number
US09403816B2

Reaction notes

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