Dimethylformamide → 4-[5-(3,5-dichlorophenyl)-5-(trifluoromethyl)-4H-isothiazol-3-yl]-2-methyl-benzamide

HRID 1522785Notes

Reaction equation

HRID 1522785 reaction equation
[Cl:1][C:2]1[CH:3]=[C:4]([C:9]2([C:24]([F:27])([F:26])[F:25])[S:13][N:12]=[C:11]([C:14]3[CH:22]=[CH:21][C:17]([C:18](O)=[O:19])=[C:16]([CH3:23])[CH:15]=3)[CH2:10]2)[CH:5]=[C:6]([Cl:8])[CH:7]=1.C[N:29](C)C=O.C(Cl)(=O)C(Cl)=O>ClCCl>[Cl:1][C:2]1[CH:3]=[C:4]([C:9]2([C:24]([F:27])([F:26])[F:25])[S:13][N:12]=[C:11]([C:14]3[CH:22]=[CH:21][C:17]([C:18]([NH2:29])=[O:19])=[C:16]([CH3:23])[CH:15]=3)[CH2:10]2)[CH:5]=[C:6]([Cl:8])[CH:7]=1

Participants

5

Reactant 3

HCID 6228DimethylformamideHCID 65578Oxalyl chlorideHCID 894445434-[5-(3,5-dichlorophenyl)-5-(trifluoromethyl)-4H-isothiazol-3-yl]-2-methyl-benzoic acid

Product 1

HCID 894445764-[5-(3,5-dichlorophenyl)-5-(trifluoromethyl)-4H-isothiazol-3-yl]-2-methyl-benzamide

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

A solution of 4-[5-(3,5-dichlorophenyl)-5-(trifluoromethyl)-4H-isothiazol-3-yl]-2-methyl-benzoic acid (1.65 g) was suspended in dichloromethane (16 mL). A catalytic amount of N,N-dimethylformamide (“DMF”) and oxalyl chloride (1.2 eq.) were added to the suspension. The reaction mixture was stirred at ambient temperature for 1.5 hour. The reaction mixture was concentrated and the residue dissolved in dry tetrahydrofuran (16 mL). To the solution was added a solution of ammonium hydroxide (8 mL, 25%). The reaction mixture was stirred at ambient temperature for two hours. It was then quenched by addition of water and extracted with ethyl acetate. The organic extract was washed with a saturated solution of sodium hydrogenocarbonate, dried over magnesium sulfate and concentrated in vacuo. The crude residue was triturated with tert-butylmethylether then the precipitate was filtered and dried under vacuo to give the title compound (841 mg) as a solid. 1H-NMR (CDCl3, 400 MHz): δ=7.50-7.61 (m, 2 H), 7.39-7.50 (m, 1 H), 7.29-7.39 (m, 1 H), 7.14-7.27 (m, 2 H), 6.40 (br. s., 1 H), 6.05 (br. s., 1 H), 4.16 (m, J=17.4, 1 H), 3.74-3.91 (m, 1 H), 2.44-2.49 (m, 3 H).

Workup

  1. concentrationThe reaction mixture was concentrated
  2. dissolutionthe residue dissolved in dry tetrahydrofuran (16 mL)
  3. additionTo the solution was added a solution of ammonium hydroxide (8 mL, 25%)
  4. stirringThe reaction mixture was stirred at ambient temperature for two hours
  5. customIt was then quenched by addition of water
  6. extractionextracted with ethyl acetate
  7. extractionThe organic extract
  8. washwas washed with a saturated solution of sodium hydrogenocarbonate
  9. dry with materialdried over magnesium sulfate
  10. concentrationconcentrated in vacuo
  11. customThe crude residue was triturated with tert-butylmethylether
  12. filtrationthe precipitate was filtered
  13. customdried under vacuo

Sources & evidence

ORD record
ord-f001d53ecba541939357d916545ac91a
Source dataset
uspto-grants-2015_07
Patent number
US09078444B2

Reaction notes

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