Phosphorus tribromide → 3-(3-Bromoprop-1-ynyl)-5-phenyl-4-(trifluoromethyl)isoxazole

HRID 1506436

반응식

HRID 1506436 반응식
[C:1]1([C:7]2[O:11][N:10]=[C:9]([C:12]#[C:13][CH2:14]O)[C:8]=2[C:16]([F:19])([F:18])[F:17])[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=1.[Br:20]P(Br)Br>ClCCl>[Br:20][CH2:14][C:13]#[C:12][C:9]1[C:8]([C:16]([F:19])([F:18])[F:17])=[C:7]([C:1]2[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=2)[O:11][N:10]=1

참가 물질

4

반응물 2

HCID 24614Phosphorus tribromide3회HCID 67167301HCID 67167301, 화합물

생성물 1

HCID 671673913-(3-Bromoprop-1-ynyl)-5-phenyl-4-(trifluoromethyl)isoxazole수율 38%

시약·촉매·용매 1

HCID 6344Dichloromethane용매4회

실험 절차

To a solution of 3-(5-phenyl-4-(trifluoromethyl)isoxazol-3-yl)prop-2-yn-1-ol (Preparation 62B, 0.465 g, 1.740 mmol) in dichloromethane (9.0 mL) at 0° C. was added a 1.0 M solution of tribromophosphine in dichloromethane (2.09 mL, 2.09 mmol). After 5 min., the ice-bath was removed, and the reaction mixture was stirred at room temperature overnight. HPLC and LCMS analysis indicated that there was still significant starting material remaining. Additional tribromophosphine (1.0 M in dichloromethane) (2.09 mL, 2.09 mmol) was added, and the reaction mixture was stirred at room temperature for 4.5 h. Additional tribromophosphine (1.0 M in dichloromethane) (2.09 mL, 2.09 mmol) was added, and the reaction mixture was stirred at room temperature over the weekend. The reaction mixture was diluted with dichloromethane, washed with a saturated aqueous solution of sodium bicarbonate, and dried over anhydrous sodium sulfate. Concentration under reduced pressure provided the crude product, which was loaded with a minimum amount of dichloromethane on a fitted funnel containing a layer of Celite topped with a layer of silica gel. The plug column was eluted with a mixture of ethyl acetate and hexane (1%-3%) to give 3-(3-bromoprop-1-ynyl)-5-phenyl-4-(trifluoromethyl)isoxazole (0.219 g, 0.663 mmol, 38% yield) as a clear, colorless oil. The product had an HPLC ret. time=2.95 min.−Column: Chromolith SpeedROD 4.6×50 mm (4 min.); Solvent A=10% MeOH, 90% H2O, 0.1% TFA; Solvent B=90% MeOH, 10% H2O, 0.1% TFA. LC/MS M+1=331.93.

후처리

  1. customthe ice-bath was removed
  2. stirringthe reaction mixture was stirred at room temperature for 4.5 h
  3. stirringthe reaction mixture was stirred at room temperature over the weekend
  4. washwashed with a saturated aqueous solution of sodium bicarbonate
  5. dry with materialdried over anhydrous sodium sulfate
  6. concentrationConcentration under reduced pressure
  7. customprovided the crude product, which
  8. additioncontaining a layer of Celite
  9. washThe plug column was eluted with a mixture of ethyl acetate and hexane (1%-3%)

출처 및 근거

ORD 기록
ord-7e315b939531446a8647a9d4a9f4c441
출처 데이터셋
uspto-grants-2015_12
특허 번호
US09216972B2

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