Carbamate → HCID 70252575, compound

HRID 2289098Notes

Reaction equation

HRID 2289098 reaction equation
C[O:2][C:3](=[O:18])[CH2:4][C:5]1[CH:10]=[CH:9][C:8]([S:11][C:12](=O)N(C)C)=[C:7]([Cl:17])[CH:6]=1.C[O-].[Na+].[C:22](=O)([O-])N.[F:26][C:27]([F:46])([F:45])[C:28]1[C:32]2[CH:33]=[CH:34][C:35]([O:40][CH2:41][CH2:42]CBr)=[C:36]([CH2:37][CH2:38][CH3:39])[C:31]=2[O:30][N:29]=1>CO>[CH3:22][CH:4]([C:5]1[CH:10]=[CH:9][C:8]([S:11][CH2:12][CH2:42][CH2:41][O:40][C:35]2[CH:34]=[CH:33][C:32]3[C:28]([C:27]([F:45])([F:26])[F:46])=[N:29][O:30][C:31]=3[C:36]=2[CH2:37][CH2:38][CH3:39])=[C:7]([Cl:17])[CH:6]=1)[C:3]([OH:2])=[O:18]

Participants

6

Reactant 4

HCID 276CarbamateHCID 10942334Sodium MethoxideHCID 12031259HCID 12031259, compoundHCID 15840683HCID 15840683, compound

Product 1

HCID 70252575HCID 70252575, compound

Reagents, catalysts & solvents 1

HCID 887MethanolSolvent2×

Conditions

Temperature
50 °C

Procedure

A solution of 3-trifluoromethyl-7-propyl-6-hydroxybenzisoxazole (2.5 grams) in 2-butanone (30 mL) was treated with 1,3-dibromopropane (4.8 mL) and potassium carbonate (5.0 grams). The mixture was refluxed for 4 hours. The reaction mixture was partitioned between isopropyl acetate and pH 4 buffer. The organic was washed once with water, then dried over magnesium sulfate. The organic was filtered and evaporated to an oil which was flitered through a silica gel plug using methylene chloride and hexane (1:2) to give 3-trifluoromethyl-7-propyl-6-(3-bromopropyloxy)-benzisoxazole. A solution of 3-chloro-4-dimethylcarbamoylthio-phenylacetic acid methyl ester (0.33 grams) in dry methanol (3.5 mL) was treated with a solution of sodium methoxide in methanol (25 wt %; 0.341 mL). The solution was refluxed for 2 hours. HPLC analysis showed the disappearance of the carbamate. The solution was allowed to cool to 50° C. 3-trifluoromethyl-7-propyl-6-(3-bromopropyloxy)-benzisoxazole (0.31 grams) was added and the solution stirred for 1 hour. The reaction was partitioned between isopropyl acetate and pH 4 buffer. The organic was washed once more with pH 4 buffer, then water. The organic was dried over magnesium sulfate, filtered and concentrated to an oil. The oil was applied to a silica gel column packed with hexane/methylene chloride (2:1). The column was eluted with this mobile phase until the product began to appear in the eluant. The mobile phase was switched to 100% methylene chloride and elution continued until all the product was recovered.

Workup

  1. temperatureThe solution was refluxed for 2 hours
  2. customThe reaction was partitioned between isopropyl acetate and pH 4 buffer
  3. washThe organic was washed once more with pH 4 buffer
  4. dry with materialThe organic was dried over magnesium sulfate
  5. filtrationfiltered
  6. concentrationconcentrated to an oil
  7. washThe column was eluted with this mobile phase until the product
  8. washThe mobile phase was switched to 100% methylene chloride and elution
  9. customwas recovered

Sources & evidence

ORD record
ord-d313d69ef0744dfcbf3728132c43b178
Source dataset
uspto-grants-2000_07
Patent number
US06090836

Reaction notes

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