Thiophenol → 2-[2,2-Difluoro-2-(4'-methoxy-biphenyl-4-yl)-ethyl]-4-hydroxy-5-phenylsulfanyl-pentanoic Acid

HRID 23760노트

반응식

HRID 23760 반응식
[F:1][C:2]([F:32])([C:18]1[CH:23]=[CH:22][C:21]([C:24]2[CH:29]=[CH:28][C:27]([O:30][CH3:31])=[CH:26][CH:25]=2)=[CH:20][CH:19]=1)[CH2:3][CH:4]1[CH2:8][CH:7]([CH2:9][S:10][C:11]2[CH:16]=[CH:15][CH:14]=[CH:13][CH:12]=2)[O:6][C:5]1=[O:17].C1C=CC(S)=CC=1.[Li]CCCC.C1C[O:48]CC1>>[F:1][C:2]([F:32])([C:18]1[CH:23]=[CH:22][C:21]([C:24]2[CH:29]=[CH:28][C:27]([O:30][CH3:31])=[CH:26][CH:25]=2)=[CH:20][CH:19]=1)[CH2:3][CH:4]([CH2:8][CH:7]([OH:48])[CH2:9][S:10][C:11]1[CH:16]=[CH:15][CH:14]=[CH:13][CH:12]=1)[C:5]([OH:6])=[O:17]

참가 물질

5

반응물 4

HCID 7969ThiophenolHCID 8028Tetrahydrofuran2회HCID 697851763-[2,2-Difluoro-2-(4'-methoxy-biphenyl-4-yl)-ethyl]-5-phenylsulfanylmethyl-dihydro-furan-2-oneHCID 178418339Butyllithium

생성물 1

HCID 101623762-[2,2-Difluoro-2-(4'-methoxy-biphenyl-4-yl)-ethyl]-4-hydroxy-5-phenylsulfanyl-pentanoic Acid

반응 조건

온도
-20 °C

실험 절차

3-[2,2-Difluoro-2-(4′-methoxy-biphenyl-4-yl)-ethyl]-5-phenylsulfanylmethyl-dihydro-furan-2-one. A solution of phenylthiol (0.65 mmol) in THF (5 mL) is treated with BuLi (0.65 mmol) at −20° C. After being stirred for 20 min at −20° C., Example 18d (0.5 mmol) in THF (5 mL) is added dropwise. The mixture is allowed to warm to 0° C. and kept at that temperature for 2 hours, then is warmed up to room temperature and stirred for 3 hours. The reaction is quenched with saturated NH4Cl, neutralized with 1N HCl and extracted with ethyl acetate. The combined organic layers are washed with brine and dried over MgSO4. The crude material obtained after evaporation of solvents is purified by flash chromatography (3/1 hexane/acetone) and recrystallized from hexane/acetone to give the desired compound as colorless needles: mp 117-118° C.

후처리

  1. temperatureto warm to 0° C.
  2. waitkept at that temperature for 2 hours
  3. temperatureis warmed up to room temperature
  4. stirringstirred for 3 hours
  5. customThe reaction is quenched with saturated NH4Cl
  6. extractionextracted with ethyl acetate
  7. washThe combined organic layers are washed with brine
  8. dry with materialdried over MgSO4
  9. customThe crude material obtained
  10. customafter evaporation of solvents
  11. customis purified by flash chromatography (3/1 hexane/acetone)
  12. customrecrystallized from hexane/acetone

출처 및 근거

ORD 기록
ord-3a148062f6b7427c94a27fdacfb08916
출처 데이터셋
uspto-grants-2005_02
특허 번호
US06852751B2

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