Oxygen → 5-(4'-Fluorophenyl)-3-(p-tolyl)-1,2,4-thiadiazole

HRID 1274210Notes

Reaction equation

HRID 1274210 reaction equation
[C:1]1([CH3:13])[CH:6]=[CH:5][C:4]([C:7]2[N:11]=[C:10](Cl)[S:9][N:8]=2)=[CH:3][CH:2]=1.[F:14][C:15]1[CH:20]=[CH:19][C:18]([Mg]Br)=[CH:17][CH:16]=1.O=O>Cl[Ni]1(Cl)[P](C2C=CC=CC=2)(C2C=CC=CC=2)CCC[P]1(C1C=CC=CC=1)C1C=CC=CC=1.C1COCC1>[F:14][C:15]1[CH:20]=[CH:19][C:18]([C:10]2[S:9][N:8]=[C:7]([C:4]3[CH:5]=[CH:6][C:1]([CH3:13])=[CH:2][CH:3]=3)[N:11]=2)=[CH:17][CH:16]=1

Participants

6

Reactant 3

HCID 977OxygenHCID 226110665-Chloro-3-p-tolyl-[1,2,4]thiadiazoleHCID 178418676HCID 178418676, compound

Product 1

HCID 226110695-(4'-Fluorophenyl)-3-(p-tolyl)-1,2,4-thiadiazoleYield 31.2%

Reagents, catalysts & solvents 2

HCID 178418745HCID 178418745, compoundCatalystHCID 8028TetrahydrofuranSolvent

Procedure

A mixture of 3-(p-tolyl)-5-chloro-1,2,4-thiadiazole (0.50 g, 2.37 mmol) and [1,3-bis(diphenylphosphino)propane]nickel(II) chloride catalyst (1.41 g, 2.61 mmol) in anhydrous THF (20 ml) is cooled in an ice-water bath. To this mixture is added slowly 4-fluorophenyl-magnesium bromide (1.0M in THF, 2.5 ml, 2.49 mmol) with exclusion of both moisture and oxygen. The mixture is allowed to warm to room temperature and stirred for 18 hours under N2. The mixture is filtered through celite and concentrated. The residue is taken up in CHCl3 (50 ml) and washed with brine (50 ml×2). The organic layer is dried over magnesium sulfate and concentrated. The residue is purified on a silica gel column, eluting with 3:7 CHCl3 :hexanes to yield 5-(4'-fluorophenyl)-3-(p-tolyl)-1,2,4-thiadiazole (0.20 g, 31%).

Workup

  1. temperatureis cooled in an ice-water bath
  2. filtrationThe mixture is filtered through celite
  3. concentrationconcentrated
  4. washwashed with brine (50 ml×2)
  5. dry with materialThe organic layer is dried over magnesium sulfate
  6. concentrationconcentrated
  7. customThe residue is purified on a silica gel column
  8. washeluting with 3:7 CHCl3

Sources & evidence

ORD record
ord-9b7338c7ac6c4deca8a43142dd43b7e3
Source dataset
uspto-grants-2000_12
Patent number
US06156776

Reaction notes

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