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

HRID 23760Notes

Reaction equation

HRID 23760 reaction equation
[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]

Participants

5

Reactant 4

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

Product 1

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

Conditions

Temperature
-20 °C

Procedure

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.

Workup

  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

Sources & evidence

ORD record
ord-3a148062f6b7427c94a27fdacfb08916
Source dataset
uspto-grants-2005_02
Patent number
US06852751B2

Reaction notes

Loading…