Sodium hydride → 1-Methyl-3-(3-spiro[m-dioxane-5,2'-oxiran]-2-yl-1,2-benzisothiazol-5-yl)-6-(trifluoromethyl)uracil

HRID 49008Notes

Reaction equation

HRID 49008 reaction equation
Br[CH2:2][C:3]1([OH:31])[CH2:8][O:7][CH:6]([C:9]2[C:13]3[CH:14]=[C:15]([N:18]4[C:23](=[O:24])[CH:22]=[C:21]([C:25]([F:28])([F:27])[F:26])[N:20]([CH3:29])[C:19]4=[O:30])[CH:16]=[CH:17][C:12]=3[S:11][N:10]=2)[O:5][CH2:4]1.[H-].[Na+].[Cl-].[NH4+]>O1CCCC1>[CH3:29][N:20]1[C:21]([C:25]([F:26])([F:27])[F:28])=[CH:22][C:23](=[O:24])[N:18]([C:15]2[CH:16]=[CH:17][C:12]3[S:11][N:10]=[C:9]([CH:6]4[O:7][CH2:8][C:3]5([CH2:2][O:31]5)[CH2:4][O:5]4)[C:13]=3[CH:14]=2)[C:19]1=[O:30]

Participants

5

Reactant 3

HCID 24758Sodium hydride2×HCID 25517Ammonium ChlorideHCID 206342383-[3-[5-(Bromomethyl)-5-hydroxy-m-dioxan-2-yl]-1,2-benzisothiazol-5-yl]-1-methyl-6-(trifluoromethyl)uracil

Product 1

HCID 206341951-Methyl-3-(3-spiro[m-dioxane-5,2'-oxiran]-2-yl-1,2-benzisothiazol-5-yl)-6-(trifluoromethyl)uracilYield 16.3%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

To a mixture of 3-[3-[5-(bromomethyl)-5-hydroxy-m-dioxan-2-yl]-1,2-benzisothiazol-5-yl]-1-methyl-6-(trifluoromethyl)uracil (0.580 g, 1.11 mmol) and tetrahydrofuran at 5° C. is added sodium hydride (60% dispersion in mineral oil, 0.0400 g, 1.11 mmol). The resultant mixture is stirred overnight at ambient temperature and treated with additional sodium hydride (0.0400 g, 1.11 mmol). The mixture is poured into saturated ammonium chloride and extracted twice with diethyl ether. The combined organic extracts are washed with 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 (0.0800 g, 16.3%, mp 203-206° C.) which is identified by NMR spectral analysis.

Workup

  1. extractionextracted twice with diethyl ether
  2. washThe combined organic extracts are washed with water and brine
  3. dry with materialdried over anhydrous magnesium sulfate
  4. concentrationconcentrated in vacuo
  5. customThe residue is chromatographed on silica gel with diethyl ether-methylene chloride

Sources & evidence

ORD record
ord-d3d1cb32c80f4771a7636593fd4bfba4
Source dataset
uspto-grants-2004_03
Patent number
US06706663B2

Reaction notes

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