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

HRID 627473Notes

Reaction equation

HRID 627473 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 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.

Workup

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

Sources & evidence

ORD record
ord-982698da522f4d6ba63d9ffbdc63b5b6
Source dataset
uspto-grants-2016_04
Patent number
US09309222B2

Reaction notes

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