Trifluoromethanesulfonic acid → 5-Bromo-2-chloro-4-hydroxybenzonitrile

HRID 46227

Reaction equation

HRID 46227 reaction equation
[Cl:1][C:2]1[CH:9]=[C:8]([OH:10])[CH:7]=[CH:6][C:3]=1[C:4]#[N:5].ClC1C(CC2SC(C3OC=CC=3)=NN=2)=CC([C@H]2[C@H](O)[C@@H](O)[C@H](O)[C@@H](CO)O2)=C(OC)C=1.OS(C(F)(F)F)(=O)=O.C1C(=O)N([Br:57])C(=O)C1>C(#N)C>[Br:57][C:7]1[C:8]([OH:10])=[CH:9][C:2]([Cl:1])=[C:3]([CH:6]=1)[C:4]#[N:5]

Participants

6

Reactant 4

HCID 62406Trifluoromethanesulfonic acidHCID 67184N-bromobutanimideHCID 5927972-Chloro-4-hydroxybenzonitrileHCID 49846233(2S,3R,4R,5S,6R)-2-(4-Chloro-5-((5-(furan-2-yl)-1,3,4-thiadiazol-2-yl)methyl)-2-methoxyphenyl)-6-(hydroxymethyl)-tetrahydro-2H-pyran-3,4,5-triol

Product 1

HCID 533304525-Bromo-2-chloro-4-hydroxybenzonitrileYield 65%

Reagents, catalysts & solvents 1

HCID 6342AcetonitrileSolvent

Procedure

To a solution of 2-chloro-4-hydroxybenzonitrile (compound 86, 10.0 g, 65.1 mmol) in acetonitrile (200 mL) was added triflic acid (10.0 mL, 71.6 mmol) and NBS (16.2 g, 91.2 mmol) at −30° C. The solution was allowed to warm up to room temperature and stirred overnight prior to quenching with saturated sodium bisulfite. The mixture was diluted with water and extracted with EtOAc. The organic layer was dried over anhydrous MgSO4, filtered and concentrated in vacuo. The crude residue was purified by column chromatography (5-40% EtOAc/hexanes) to yield title compound (9.80 g, 65%) as a white solid.

Workup

  1. customto quenching with saturated sodium bisulfite
  2. additionThe mixture was diluted with water
  3. extractionextracted with EtOAc
  4. dry with materialThe organic layer was dried over anhydrous MgSO4
  5. filtrationfiltered
  6. concentrationconcentrated in vacuo
  7. customThe crude residue was purified by column chromatography (5-40% EtOAc/hexanes)

Sources & evidence

ORD record
ord-0711056d217843be94d291a1aa661bdd
Source dataset
uspto-grants-2013_09
Patent number
US08541380B2

Linked notes

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