Triethylamine → 6-Methoxy-benzo[d]isothiazole-3-carboxylic acid (4-fluoro-3-trifluoromethyl-phenyl)-amide

HRID 556354Notes

Reaction equation

HRID 556354 reaction equation
[CH3:1][O:2][C:3]1[CH:14]=[CH:13][C:6]2[C:7]([C:10]([OH:12])=O)=[N:8][S:9][C:5]=2[CH:4]=1.[F:15][C:16]1[CH:22]=[CH:21][C:19]([NH2:20])=[CH:18][C:17]=1[C:23]([F:26])([F:25])[F:24].CCN(CC)CC.CCCP(=O)=O>CN(C=O)C.CCOC(C)=O.O>[F:15][C:16]1[CH:22]=[CH:21][C:19]([NH:20][C:10]([C:7]2[C:6]3[CH:13]=[CH:14][C:3]([O:2][CH3:1])=[CH:4][C:5]=3[S:9][N:8]=2)=[O:12])=[CH:18][C:17]=1[C:23]([F:24])([F:25])[F:26]

Participants

8

Reactant 4

HCID 8471TriethylamineHCID 753774-Fluoro-3-(trifluoromethyl)anilineHCID 16167369Propylphosphoric anhydride2×HCID 666368056-Methoxybenzo[d]isothiazole-3-carboxylic acid

Product 1

HCID 669929426-Methoxy-benzo[d]isothiazole-3-carboxylic acid (4-fluoro-3-trifluoromethyl-phenyl)-amide

Reagents, catalysts & solvents 3

HCID 962WaterSolventHCID 6228DimethylformamideSolventHCID 8857Ethyl AcetateSolvent

Procedure

209 mg (1.00 mMol) 6-methoxy-benzo[d]isothiazole-3-carboxylic acid (preparation see: WO 2004/029050, Procedure N), 269 mg (1.5 mMol) 4-fluoro-3-trifluoromethyl-aniline and 1.4 ml (10 mMol) Et3N are dissolved in 5 ml of dry DMF and cooled in an ice-bath. Then a solution of 1.17 ml (50% in DMF; 2.0 mMol) propylphosphonic anhydride is added. The mixture is stirred for 15 h at rt, when another 0.58 ml of propylphosphonic anhydride are added. After 2 h, the reaction mixture is poured into water and EtOAc, the aq. phase separated off and extracted twice with EtOAc. The organic layers are washed twice with water and brine, dried (Na2SO4) and partially concentrated. Addition of hexane precipitates the title compound: m.p.: 157° C.; MS: [M+1]+=371.

Workup

  1. temperaturecooled in an ice-bath
  2. waitAfter 2 h
  3. customthe aq. phase separated off
  4. extractionextracted twice with EtOAc
  5. washThe organic layers are washed twice with water and brine
  6. dry with materialdried (Na2SO4)
  7. concentrationpartially concentrated
  8. additionAddition of hexane
  9. customprecipitates the title compound

Sources & evidence

ORD record
ord-c747789c82d94f079eb4aaf867528a28
Source dataset
uspto-grants-2011_11
Patent number
US08058276B2

Reaction notes

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