Acetone → {4-[(2r,3r)-3-{[2-(4-Ethoxyphenyl)-2-oxoethyl]thio}-1-(4-fluorophenyl)-4-oxoazetidin-2-yl]phenoxy}acetic acid

HRID 254108Notes

Reaction equation

HRID 254108 reaction equation
[F:1][C:2]1[CH:7]=[CH:6][C:5]([N:8]2[C:11](=[O:12])[C@H:10]([S:13]SC3C([N+]([O-])=O)=CC=CN=3)[C@H:9]2[C:24]2[CH:38]=[CH:37][C:27]([O:28][CH2:29][C:30]([O:32]C(C)(C)C)=[O:31])=[CH:26][CH:25]=2)=[CH:4][CH:3]=1.C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.BrCC([C:62]1[CH:67]=[CH:66][CH:65]=[C:64]([O:68][CH2:69][CH3:70])[CH:63]=1)=O.CCN(CC)CC.[CH3:78][C:79](C)=[O:80]>C(Cl)Cl.C(O)=O.O>[CH2:69]([O:68][C:64]1[CH:63]=[CH:62][C:67]([C:79](=[O:80])[CH2:78][S:13][C@H:10]2[C:11](=[O:12])[N:8]([C:5]3[CH:6]=[CH:7][C:2]([F:1])=[CH:3][CH:4]=3)[C@@H:9]2[C:24]2[CH:38]=[CH:37][C:27]([O:28][CH2:29][C:30]([OH:32])=[O:31])=[CH:26][CH:25]=2)=[CH:66][CH:65]=1)[CH3:70]

Participants

9

Reactant 5

HCID 180AcetoneHCID 8471TriethylamineHCID 11776TriphenylphosphineHCID 226410062-Bromo-1-(3-ethoxyphenyl)ethanoneHCID 86639220{4-[(2R,3R)-1-(4-fluoro-phenyl)-3-(3-nitro-pyridin-2-yldisulfanyl)-4-oxo-azetidin-2-yl]-phenoxy}-acetic acid tert-butyl ester

Product 1

HCID 66843344{4-[(2r,3r)-3-{[2-(4-Ethoxyphenyl)-2-oxoethyl]thio}-1-(4-fluorophenyl)-4-oxoazetidin-2-yl]phenoxy}acetic acidYield 57%

Reagents, catalysts & solvents 3

HCID 284Formic AcidSolventHCID 962WaterSolventHCID 6344DichloromethaneSolvent

Procedure

tert-Butyl (4-{(2R,3R)-1-(4-fluorophenyl)-3-[(3-nitropyridin-2-yl)dithio]-4-oxoazetidin-2-yl}phenoxy)acetate (0.25 g, 0.45 mmol) was dissolved in acetone (10 ml) at room temperature. Water (2.5 ml) and triphenyl phosphine (0.12 g, 0.45 mmol) were added. The mixture was stirred at room temperature for 15 minutes and then concentrated under reduced pressure to afford the crude thiol as a brown oil. This crude thiol was immediately dissolved in CH2Cl2 (10 ml) and (2-bromo-3′-ethoxy acetophenone (0.22 g, 0.90 mmol) was added, followed by Et3N (0.13 ml, 0.90 mmol). The mixture was stirred at room temperature for 19 hours, concentrated under reduced pressure and purified by flash-chromatography (Hex:EtOAc 3:1). This afforded a colourless oil that was dissolved in formic acid (10 ml) and stirred at ambient temperature for 18 hours. Concentration under reduced pressure and purification by flash-chromatography (hex:acetone:formic acid 60:40:0.1) afforded 0.13 g (57%) of the desired product as a pale yellow solid.

Workup

  1. concentrationconcentrated under reduced pressure
  2. customto afford the crude thiol as a brown oil
  3. stirringThe mixture was stirred at room temperature for 19 hours
  4. concentrationconcentrated under reduced pressure
  5. custompurified by flash-chromatography (Hex:EtOAc 3:1)
  6. customThis afforded a colourless oil that
  7. stirringstirred at ambient temperature for 18 hours
  8. concentrationConcentration
  9. customunder reduced pressure and purification by flash-chromatography (hex:acetone:formic acid 60:40:0.1)

Sources & evidence

ORD record
ord-6592d387d65f492686466141198b1806
Source dataset
uspto-grants-2011_01
Patent number
US07871998B2

Reaction notes

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