Toluene → 3-[3-(3,6-Dihydro-4,6,6-trimethyl-2H-pyran-2-yl)-1,2-benzisothiazol-5-yl]-1-methyl-6-(trifluoromethyl)uracil

HRID 49010Notes

Reaction equation

HRID 49010 reaction equation
[CH3:1][N:2]1[C:7]([C:8]([F:11])([F:10])[F:9])=[CH:6][C:5](=[O:12])[N:4]([C:13]2[CH:14]=[CH:15][C:16]3[S:20][N:19]=[C:18]([CH:21]=[O:22])[C:17]=3[CH:23]=2)[C:3]1=[O:24].[CH3:25][C:26](O)([CH2:28][C:29]([CH3:32])(O)[CH3:30])[CH3:27].C1(C)C=CC(S(O)(=O)=O)=CC=1.C1(C)C=CC=CC=1>C(OCC)C.C(OCC)(=O)C.O>[CH3:25][C:26]1[CH2:27][CH:21]([C:18]2[C:17]3[CH:23]=[C:13]([N:4]4[C:5](=[O:12])[CH:6]=[C:7]([C:8]([F:9])([F:10])[F:11])[N:2]([CH3:1])[C:3]4=[O:24])[CH:14]=[CH:15][C:16]=3[S:20][N:19]=2)[O:22][C:29]([CH3:32])([CH3:30])[CH:28]=1

Participants

8

Reactant 4

HCID 1140TolueneHCID 6101p-Toluenesulfonic acidHCID 1411532,4-Pentanediol, 2,4-dimethyl-HCID 178523685-[3,6-dihydro-3-methyl-2,6-dioxo-4-(trifluoromethyl)-1(2H)-pyrimidinyl]-1, 2-benzisothiazole-3-carboxaldehyde

Product 1

HCID 206342123-[3-(3,6-Dihydro-4,6,6-trimethyl-2H-pyran-2-yl)-1,2-benzisothiazol-5-yl]-1-methyl-6-(trifluoromethyl)uracilYield 31.4%

Reagents, catalysts & solvents 3

HCID 962WaterSolventHCID 3283Diethyl EtherSolventHCID 8857Ethyl AcetateSolvent

Procedure

A mixture of 5-[3,6-dihydro-3-methyl-2,6-dioxo-4-(trifluoromethyl)-1(2H)-pyrimidinyl]-1, 2-benzisothiazole-3-carboxaldehyde(0.500 g, 0.00141 mol), 2,4-dimethyl-2,4-pentanediol (0.260 g, 0.00183 mol), p-toluenesulfonic acid (0.0100 g, 0.000071 mol) and toluene is stirred overnight at reflux with azeotropic removal of water. The mixture is cooled to room temperature, diluted with diethyl ether and ethyl acetate and washed with two prortions of water and brine. The organic layer is dried and concentrated in vacuo to a brown oil, which is chromatographed on silica gel with ethyl acetate-hexanes to afford the title compound as a white solid (0.200 g, 31.4%, mp 88-92° C.) which is characterized by NMR spectral analysis.

Workup

  1. washwashed with two prortions of water and brine
  2. customThe organic layer is dried
  3. concentrationconcentrated in vacuo to a brown oil, which
  4. customis chromatographed on silica gel with ethyl acetate-hexanes

Sources & evidence

ORD record
ord-ca22450bb37740998ec0ebe68c4f1155
Source dataset
uspto-grants-2004_03
Patent number
US06706663B2

Reaction notes

Loading…