Phosphorus oxychloride → HCID 118006027, compound

HRID 926553Notes

Reaction equation

HRID 926553 reaction equation
[CH2:1]([C:8]1[C:9]([C:20]([F:23])([F:22])[F:21])=[N:10][C:11]2[C:16]([C:17]=1O)=[CH:15][C:14]([I:19])=[CH:13][CH:12]=2)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.P(Cl)(Cl)([Cl:26])=O.C(C1C(C(F)(F)F)=NC2C(C=1Cl)=CC=CC=2)C1C=CC=CC=1>>[CH2:1]([C:8]1[C:9]([C:20]([F:23])([F:22])[F:21])=[N:10][C:11]2[C:16]([C:17]=1[Cl:26])=[CH:15][C:14]([I:19])=[CH:13][CH:12]=2)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1

Participants

4

Reactant 3

HCID 24813Phosphorus oxychlorideHCID 118006593HCID 118006593, compoundHCID 178515536HCID 178515536, compound

Product 1

HCID 118006027HCID 118006027, compound

Procedure

A solution of 3-benzyl-6-iodo-2-(trifluoromethyl)quinolin-4-ol (6.10 g, 14.2 mmol, Intermediate 71: step a) in phosphoryl trichloride (18 mL, 194 mmol) was heated at 110° C. for 3 hours, then concentrated in vacuo. After cooling down to room temperature, ice-water and DCM were added to the residue, and the mixture was basified at 4° C. by the addition of 50% aqueous NaOH and concentrated NH4OH to pH 9. The organic layer was separated and the aqueous layer was extracted with DCM. The combined organic phases were dried (Na2SO4), filtered, concentrated, and purified by flash column chromatography (silica gel, 2-6% EtOAc in heptanes), affording a mixture of the title compound and 3-benzyl-4-chloro-2-(trifluoromethyl)quinoline in ˜2:1 ratio.

Workup

  1. concentrationconcentrated in vacuo
  2. additionice-water and DCM were added to the residue
  3. additionthe mixture was basified at 4° C. by the addition of 50% aqueous NaOH and concentrated NH4OH to pH 9
  4. customThe organic layer was separated
  5. extractionthe aqueous layer was extracted with DCM
  6. dry with materialThe combined organic phases were dried (Na2SO4)
  7. filtrationfiltered
  8. concentrationconcentrated
  9. custompurified by flash column chromatography (silica gel, 2-6% EtOAc in heptanes)
  10. customaffording

Sources & evidence

ORD record
ord-1ceb2ac9c1d4437290d2e652692c25ee
Source dataset
uspto-grants-2016_03
Patent number
US09284308B2

Reaction notes

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