Sodium hydride → 6-chloro-5-hydroxvl-2-(trifluoromethyl)-2H-chromene-3-carboxylic acid

HRID 855142노트

반응식

HRID 855142 반응식
[Cl:1][C:2]1[C:3](F)=[C:4]2[C:9](=[CH:10][CH:11]=1)[O:8][CH:7]([C:12]([F:15])([F:14])[F:13])[C:6]([C:16]([O:18]CC)=[O:17])=[CH:5]2.CS(CCO)(=O)=[O:24].[H-].[Na+]>CN(C=O)C>[Cl:1][C:2]1[C:3]([OH:24])=[C:4]2[C:9](=[CH:10][CH:11]=1)[O:8][CH:7]([C:12]([F:15])([F:14])[F:13])[C:6]([C:16]([OH:18])=[O:17])=[CH:5]2

참가 물질

5

반응물 3

HCID 24758Sodium hydrideHCID 848342-(Methylsulfonyl)ethanolHCID 58934464ethyl 6-chloro-5-fluoro-2-(trifluoromethyl)-2H-chromene-3-carboxylate

생성물 1

HCID 589344716-chloro-5-hydroxvl-2-(trifluoromethyl)-2H-chromene-3-carboxylic acid

시약·촉매·용매 1

HCID 6228Dimethylformamide용매

실험 절차

To the mixture of ethyl 6-chloro-5-fluoro-2-(trifluoromethyl)-2H-chromene-3-carboxylate (2g, 6.2 mmol) and 2-methylsulfonylethanol (2.3 g, 18.5 mmol) in 40 mL of dry DMF at 0° C. was added sodium hydride (60% mineral oil suspesion, 1.48 g, 37.2 mmol) slowly with stirring. Bubbling was observed during the process. Then the resulting black solution was stirred at room temperature for three hrs. LC-MS indicated that no any more starting material was observed. The reaction was poured into ice/aqueous ammonium chloride mixture. The product was extracted with ethyl acetate, and the resulting organic solution was washed with brine, and dried over anhydrous magnesium sulfate. After removing the volatiles, the residue was purified on silica gel column with 1:1 EtOAc/hexane+1% HOAc. The product was obtained as colorless oil, 0.8 g. Part of the product was further purified on reverse phase HPLC and gave an off-white solid. LC-MS (ES+) 295.2(M+1, 100). 1H NMR (CD3OD/300 MHz) 8.11(s, 1H), 7.30(d, J=8.7 Hz, 1H), 6.53(d, J=9.0 Hz, 1 H), 5.75(q, J=7.5 Hz, 1 H),. 19F NMR(CDCl3/300 MHz) −80.31 (d, J=7.1 Hz). High resolution MS (ES−): m/e calc. For C15H6ClF3O4: 292.9828(M−H), found: 292.9853.

후처리

  1. customBubbling
  2. stirringThen the resulting black solution was stirred at room temperature for three hrs
  3. additionThe reaction was poured into ice/aqueous ammonium chloride mixture
  4. extractionThe product was extracted with ethyl acetate
  5. washthe resulting organic solution was washed with brine
  6. dry with materialdried over anhydrous magnesium sulfate
  7. customAfter removing the volatiles
  8. customthe residue was purified on silica gel column with 1:1 EtOAc/hexane+1% HOAc
  9. customThe product was obtained as colorless oil, 0.8 g
  10. customPart of the product was further purified on reverse phase HPLC
  11. customgave an off-white solid

출처 및 근거

ORD 기록
ord-3cb08cee5c6143c68e3e838947c06a71
출처 데이터셋
uspto-grants-2007_08
특허 번호
US07259266B2

반응 노트

불러오는 중…