Triphenylphosphine Oxide → 2-(5-{3-[(1S)-2-Methoxy-1-methylethoxy]-5-[4-(methylsulfonyl)phenoxy]phenyl}-1H-pyrrol-2-yl)-4,5-dihydro-1,3-thiazole

HRID 909469Notes

Reaction equation

HRID 909469 reaction equation
C1(P(=O)(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.FC(F)(F)S(OS(C(F)(F)F)(=O)=O)(=O)=O.[CH3:36][O:37][CH2:38][C@H:39]([CH3:88])[O:40][C:41]1[CH:42]=[C:43]([C:58]2[NH:62][C:61]([C:63]([NH:65][CH2:66][CH2:67][S:68]C(C3C=CC=CC=3)(C3C=CC=CC=3)C3C=CC=CC=3)=O)=[CH:60][CH:59]=2)[CH:44]=[C:45]([O:47][C:48]2[CH:53]=[CH:52][C:51]([S:54]([CH3:57])(=[O:56])=[O:55])=[CH:50][CH:49]=2)[CH:46]=1>ClCCl>[CH3:36][O:37][CH2:38][C@H:39]([CH3:88])[O:40][C:41]1[CH:42]=[C:43]([C:58]2[NH:62][C:61]([C:63]3[S:68][CH2:67][CH2:66][N:65]=3)=[CH:60][CH:59]=2)[CH:44]=[C:45]([O:47][C:48]2[CH:53]=[CH:52][C:51]([S:54]([CH3:57])(=[O:56])=[O:55])=[CH:50][CH:49]=2)[CH:46]=1

Participants

5

Reactant 3

HCID 13097Triphenylphosphine OxideHCID 67749Trifluoromethanesulfonic anhydrideHCID 666813995-{3-[(1S)-2-Methoxy-1-methylethoxy]-5-[4-(methylsulfonyl)phenoxy]phenyl}-N-[2-(tritylthio)ethyl]-1H-pyrrole-2-carboxamide

Product 1

HCID 580654612-(5-{3-[(1S)-2-Methoxy-1-methylethoxy]-5-[4-(methylsulfonyl)phenoxy]phenyl}-1H-pyrrol-2-yl)-4,5-dihydro-1,3-thiazoleYield 90%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent2×

Procedure

Triphenylphosphine oxide (2.41 g, 8.7 mmol) was dissolved in dichloromethane (20 mL), and trifluoromethanesulfonic anhydride (0.73 mL, 4.3 mmol) was added dropwise slowly at 0° C. After stirring for 10 minutes, a dichloromethane (15 mL) solution of 5-{3-[(1S)-2-methoxy-1-methylethoxy]-5-[4-(methylsulfonyl)phenoxy]phenyl}-N[2-(tritylthio)ethyl]-1H-pyrrole-2-carboxamide synthesized in Example (25b) was added. After reaction solution was stirred at room temperature for 30 minutes, the solvent was distilled off under reduced pressure, a saturated aqueous sodium hydrogencarbonate solution was added, and extraction was carried out with ethyl acetate (200 mL). The organic layer was washed with saturated brine, and dried over anhydrous magnesium sulfate. The solvent was distilled off under reduced pressure, and the resulting residue was purified using silica gel column chromatography (elution solvent: ethyl acetate/hexane=50%-80%) to afford the desired product (636 mg, yield 90%) as a white solid.

Workup

  1. customAfter reaction solution
  2. stirringwas stirred at room temperature for 30 minutes
  3. distillationthe solvent was distilled off under reduced pressure
  4. additiona saturated aqueous sodium hydrogencarbonate solution was added
  5. extractionextraction
  6. washThe organic layer was washed with saturated brine
  7. dry with materialdried over anhydrous magnesium sulfate
  8. distillationThe solvent was distilled off under reduced pressure
  9. customthe resulting residue was purified
  10. washsilica gel column chromatography (elution solvent: ethyl acetate/hexane=50%-80%)

Sources & evidence

ORD record
ord-7d84d5f14f8e443189a313505a2e724b
Source dataset
uspto-grants-2011_09
Patent number
US08017610B2

Reaction notes

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