7-bromo-3-fluoro-2-methoxy-9H-xanthen-9-one → 7-bromo-3-fluoro-2-methoxy-9-methyl-9H-xanthen-9-ol

HRID 335918

반응식

HRID 335918 반응식
[Br:1][C:2]1[CH:15]=[C:14]2[C:5]([O:6][C:7]3[CH:8]=[C:9]([F:19])[C:10]([O:17][CH3:18])=[CH:11][C:12]=3[C:13]2=[O:16])=[CH:4][CH:3]=1.[CH3:20][Mg]Cl>C1COCC1>[Br:1][C:2]1[CH:15]=[C:14]2[C:5]([O:6][C:7]3[CH:8]=[C:9]([F:19])[C:10]([O:17][CH3:18])=[CH:11][C:12]=3[C:13]2([CH3:20])[OH:16])=[CH:4][CH:3]=1

참가 물질

4

반응물 2

HCID 584662337-bromo-3-fluoro-2-methoxy-9H-xanthen-9-oneHCID 178418332HCID 178418332, 화합물

생성물 1

HCID 673836947-bromo-3-fluoro-2-methoxy-9-methyl-9H-xanthen-9-ol수율 100.4%

시약·촉매·용매 1

HCID 8028Tetrahydrofuran용매

실험 절차

To a suspension of 7-bromo-3-fluoro-2-methoxy-9H-xanthen-9-one (25 g, 73.4 mmol) in THF (500 mL) was added MeMgCl (2.0 equiv. 146.75 mmol, 48.9 mL, 3.0 M solution in THF) at −20° C. (internal temp) slowly over 30 minutes. The resulting mixture was allowed to reach ambient temperature where it was maintained for 12 hours. The reaction was quenched by adding saturated NH4Cl. The phases were separated and the aqueous layer was extracted with EtOAc (2×300 mL). The combined organic extracts were washed with brine, dried over Na2SO4, filtered and concentrated to afford 25 g of 7-bromo-3-fluoro-2-methoxy-9-methyl-9H-xanthen-9-ol that was used in the next step without further purification. A solution of the derived alcohol (25 g) was dissolved in DCM (300 mL) and pPTS (250 mg, 0.995 mmol) was added. The mixture was heated to reflux for 2 hours at which time the reaction was cooled to rt and washed with NaHCO3 (100 mL). The layers were separated and the organic layer was washed with brine, dried over Na2SO4, filtered and concentrated. The resulting residue was purified via chromatography (hexanes/DCM, 3:1) to provide 7-bromo-3-fluoro-2-methoxy-9-methylene-9H-xanthene as an orange solid.

후처리

  1. customto reach ambient temperature
  2. temperaturewas maintained for 12 hours
  3. customThe reaction was quenched
  4. additionby adding saturated NH4Cl
  5. customThe phases were separated
  6. extractionthe aqueous layer was extracted with EtOAc (2×300 mL)
  7. washThe combined organic extracts were washed with brine
  8. dry with materialdried over Na2SO4
  9. filtrationfiltered
  10. concentrationconcentrated

출처 및 근거

ORD 기록
ord-bd8aaf5bf4904f1588129784b038c5c5
출처 데이터셋
uspto-grants-2014_11
특허 번호
US08883782B2

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