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

HRID 23760ノート

反応式

HRID 23760 の反応式
[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]

参加物

5

反応物 4

HCID 7969ThiophenolHCID 8028Tetrahydrofuran2 回HCID 697851763-[2,2-Difluoro-2-(4'-methoxy-biphenyl-4-yl)-ethyl]-5-phenylsulfanylmethyl-dihydro-furan-2-oneHCID 178418339Butyllithium

生成物 1

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

反応条件

温度
-20 °C

実験手順

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.

後処理

  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

出典と根拠

ORDレコード
ord-3a148062f6b7427c94a27fdacfb08916
出典データセット
uspto-grants-2005_02
特許番号
US06852751B2

反応ノート

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