Carbamate → Methyl 3-chloro-4-(3-(7-propyl-3-trifluoromethyl-6-benz-[4,5]-isoxazoloxy)propylthio) phenylacetic acid

HRID 2289098노트

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HRID 2289098 반응식
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]

참가 물질

6

반응물 4

HCID 276CarbamateHCID 10942334Sodium MethoxideHCID 120312593-Trifluoromethyl-7-propyl-6-(3-bromopropyloxy)-benzisoxazoleHCID 15840683HCID 15840683, 화합물

생성물 1

HCID 70252575Methyl 3-chloro-4-(3-(7-propyl-3-trifluoromethyl-6-benz-[4,5]-isoxazoloxy)propylthio) phenylacetic acid

시약·촉매·용매 1

HCID 887Methanol용매2회

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온도
50 °C

실험 절차

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.

후처리

  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

출처 및 근거

ORD 기록
ord-d313d69ef0744dfcbf3728132c43b178
출처 데이터셋
uspto-grants-2000_07
특허 번호
US06090836

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