Hydrochloric Acid → 3-[3-[3-(Hydroxymethyl)-2-thienyl]-1,2-benzisothiazol-5-yl]-1-methyl-6-(trifluoromethyl)uracil

HRID 48970Notes

Reaction equation

HRID 48970 reaction equation
Br[CH2:2][C:3]1[CH:7]=[CH:6][S:5][C:4]=1[C:8]1[C:12]2[CH:13]=[C:14]([N:17]3[C:22](=[O:23])[CH:21]=[C:20]([C:24]([F:27])([F:26])[F:25])[N:19]([CH3:28])[C:18]3=[O:29])[CH:15]=[CH:16][C:11]=2[S:10][N:9]=1.CS(C)=[O:32].N([O-])=O.[Na+].Cl>O.C(O)(=O)C>[OH:32][CH2:2][C:3]1[CH:7]=[CH:6][S:5][C:4]=1[C:8]1[C:12]2[CH:13]=[C:14]([N:17]3[C:22](=[O:23])[CH:21]=[C:20]([C:24]([F:27])([F:26])[F:25])[N:19]([CH3:28])[C:18]3=[O:29])[CH:15]=[CH:16][C:11]=2[S:10][N:9]=1

Participants

7

Reactant 4

HCID 313Hydrochloric AcidHCID 679Dimethyl SulfoxideHCID 206342133-[3-[3-(Bromomethyl)-2-thienyl]-1,2-benzisothiazol-5-yl]-1-methyl-6-(trifluoromethyl)uracilHCID 23668193Sodium Nitrite

Product 1

HCID 206342163-[3-[3-(Hydroxymethyl)-2-thienyl]-1,2-benzisothiazol-5-yl]-1-methyl-6-(trifluoromethyl)uracilYield 38.3%

Reagents, catalysts & solvents 2

HCID 176Acetic AcidSolventHCID 962WaterSolvent

Procedure

To a mixture of 3-[3-[3-(bromomethyl)-2-thienyl]-1,2-benzisothiazol-5-yl]-1-methyl-6-(trifluoromethyl)uracil(0.840 g, 1.67 mmol), dimethylsulfoxide and sodium nitrite is added glacial acetic acid. The resultant mixture is stirred overnight at 50° C., cooled and acidified with 10% aqueous hydrochloric acid. The mixture is diluted with water and extracted twice with ethyl acetate. The combined organic layers are washed with saturated sodium carbonate, water and brine, dried over anhydrous magnesium sulfate and concentrated in vacuo. The residue is chromatographed on silica gel with diethyl ether-methylene chloride to afford the title compound as an off-white solid (0.290 g, 38.3%, mp 168-169° C.) which is identified by IR and NMR spectral analysis.

Workup

  1. temperaturecooled
  2. extractionextracted twice with ethyl acetate
  3. washThe combined organic layers are washed with saturated sodium carbonate, water and brine
  4. dry with materialdried over anhydrous magnesium sulfate
  5. concentrationconcentrated in vacuo
  6. customThe residue is chromatographed on silica gel with diethyl ether-methylene chloride

Sources & evidence

ORD record
ord-ebc9532d980743fda8713e773f950165
Source dataset
uspto-grants-2004_03
Patent number
US06706663B2

Reaction notes

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