O-Xylene → 1,2-Dihydro-4-[(4-ethylaminophenyl)methyl]-5-(trifluoromethyl)-3H-pyrazol-3-one

HRID 257849노트

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HRID 257849 반응식
B.C1COCC1.[C:7]([NH:10][C:11]1[CH:16]=[CH:15][C:14]([CH2:17][C:18]2[C:19](=[O:27])[N:20]=[N:21][C:22]=2[C:23]([F:26])([F:25])[F:24])=[CH:13][CH:12]=1)(=O)[CH3:8].C(NC1C=CC(CCl)=CC=1)(=O)C.C1(C)C(C)=CC=CC=1>O1CCCC1>[CH2:7]([NH:10][C:11]1[CH:16]=[CH:15][C:14]([CH2:17][C:18]2[C:19](=[O:27])[NH:20][NH:21][C:22]=2[C:23]([F:25])([F:24])[F:26])=[CH:13][CH:12]=1)[CH3:8]

참가 물질

6

반응물 4

HCID 7237O-XyleneHCID 148705Acetamide, N-(4-(chloromethyl)phenyl)-HCID 2723981Borane;tetrahydrofuranHCID 197820874-[(4-acetamidophenyl)methyl]-5-(trifluoromethyl)-3H-pyrazol-3-one

생성물 1

HCID 107794671,2-Dihydro-4-[(4-ethylaminophenyl)methyl]-5-(trifluoromethyl)-3H-pyrazol-3-one

시약·촉매·용매 1

HCID 8028Tetrahydrofuran용매2회

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온도
-30 °C

실험 절차

A solution of borane-THF complex (188 mL, 1M solution in tetrahydrofuran), diluted with 200 mL tetrahydrofuran, was cooled to -30° C. under N2 atmosphere. A solution of 4-[(4-acetamidophenyl)methyl]-5-(trifluoromethyl)-3H-pyrazol-3-one (6 g, prepared as in Example 1 (except that 4-acetamidobenzylchloride was reacted with the β-keto ester anion in refluxing xylene) in tetrahydrofuran (300 mL) was added over 0.75 hours and the mixture allowed to warm gradually to ambient temperature with stirring for 15 hours. The reaction mixture was refluxed for 3 hours, then cooled in ice and quenched with aqueous sodium hydroxide solution (24 mL, 2.5N). The mixture was stirred for 2 hours at ice temperature and 15 hours at room temperature. Volatile materials were removed in vacuo on the rotary evaporator. The residue was solubilized in distilled water, brought to pH 7 with dilute, aqueous HCl solution and extracted with ethyl acetate. The extracts were washed with saturated brine solution, dried over MgSO4, filtered and concentrated. The residue was dissolved in isopropyl alcohol saturated with anhydrous HCl and cooled in ice. The precipitate was collected on a suction funnel and dried under vacuum (abderhalden apparatus) to afford the title compound as a pale yellow glass; sinters at 104° C., liquefies 169°-171° C.

후처리

  1. additionwas added over 0.75 hours
  2. temperatureto warm gradually to ambient temperature
  3. temperatureThe reaction mixture was refluxed for 3 hours
  4. temperaturecooled in ice
  5. customquenched with aqueous sodium hydroxide solution (24 mL, 2.5N)
  6. stirringThe mixture was stirred for 2 hours at ice temperature and 15 hours at room temperature
  7. customVolatile materials were removed in vacuo on the rotary evaporator
  8. additionwith dilute
  9. extractionaqueous HCl solution and extracted with ethyl acetate
  10. washThe extracts were washed with saturated brine solution
  11. dry with materialdried over MgSO4
  12. filtrationfiltered
  13. concentrationconcentrated
  14. dissolutionThe residue was dissolved in isopropyl alcohol saturated with anhydrous HCl
  15. temperaturecooled in ice
  16. customThe precipitate was collected on a suction funnel
  17. customdried under vacuum (abderhalden apparatus)

출처 및 근거

ORD 기록
ord-918b29f42e5a4b4b96c4a8058e47e77e
출처 데이터셋
uspto-grants-1993_11
특허 번호
US05264451

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