Potassium Carbonate → Methyl (4S)-2-[5-(3-[(1S)-2-methoxy-1-methylethoxy]-5-{[6-(methylsulfonyl)pyridin-3-yl]oxy}phenyl)-1H-pyrrol-2-yl]-4,5-dihydro-1,3-oxazole-4-carboxylate

HRID 909577Notes

Reaction equation

HRID 909577 reaction equation
[CH3:1][O:2][CH2:3][C@H:4]([CH3:38])[O:5][C:6]1[CH:7]=[C:8]([C:23]2[NH:27][C:26]([C:28]([NH:30][C@H:31]([C:34]([O:36][CH3:37])=[O:35])[CH2:32][OH:33])=O)=[CH:25][CH:24]=2)[CH:9]=[C:10]([O:12][C:13]2[CH:14]=[N:15][C:16]([S:19]([CH3:22])(=[O:21])=[O:20])=[CH:17][CH:18]=2)[CH:11]=1.COCCN(S(F)(F)F)CCOC.C(=O)([O-])[O-].[K+].[K+].C(=O)([O-])O.[Na+]>C(Cl)Cl>[CH3:1][O:2][CH2:3][C@H:4]([CH3:38])[O:5][C:6]1[CH:7]=[C:8]([C:23]2[NH:27][C:26]([C:28]3[O:33][CH2:32][C@@H:31]([C:34]([O:36][CH3:37])=[O:35])[N:30]=3)=[CH:25][CH:24]=2)[CH:9]=[C:10]([O:12][C:13]2[CH:14]=[N:15][C:16]([S:19]([CH3:22])(=[O:21])=[O:20])=[CH:17][CH:18]=2)[CH:11]=1

Participants

6

Reactant 4

HCID 11430Potassium CarbonateHCID 516892Sodium BicarbonateHCID 2734690(Bis(2-methoxyethyl)amino)sulfur trifluorideHCID 66682685Methyl N-{[5-(3-[(1S)-2-methoxy-1-methylethoxy]-5-{[6-(methylsulfonyl)pyridin-3-yl]oxy}phenyl)-1H-pyrrol-2-yl]carbonyl}-L-serinate

Product 1

HCID 66681625Methyl (4S)-2-[5-(3-[(1S)-2-methoxy-1-methylethoxy]-5-{[6-(methylsulfonyl)pyridin-3-yl]oxy}phenyl)-1H-pyrrol-2-yl]-4,5-dihydro-1,3-oxazole-4-carboxylateYield 93.1%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

Methyl N-{[5-(3-[(1S)-2-methoxy-1-methylethoxy]-5-{[6-(methylsulfonyl)pyridin-3-yl]oxy}phenyl)-1H-pyrrol-2-yl]carbonyl}-L-serinate (1.91 g, 3.57 mmol) synthesized in Example (86a) was dissolved in methylene chloride (40 mL), and bis(2-methoxyethyl)aminosulfur trifluoride (0.85 mL, 4.64 mmol) was added dropwise at −78° C. After stirring for 30 minutes under nitrogen atmosphere, potassium carbonate (0.74 g, 5.35 mmol) was added, and stirring was carried out at 0° C. for 10 minutes, followed by further stirring at room temperature for 3 hours. A saturated aqueous sodium hydrogencarbonate solution (30 mL) was added, followed by extraction with methylene chloride (100 mL), and 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=30%-70%) to afford the desired compound (1.76 g, 93%) as a white powder.

Workup

  1. stirringstirring
  2. waitwas carried out at 0° C. for 10 minutes
  3. stirringby further stirring at room temperature for 3 hours
  4. extractionfollowed by extraction with methylene chloride (100 mL)
  5. washthe organic layer was washed with saturated brine
  6. dry with materialdried over anhydrous magnesium sulfate
  7. distillationThe solvent was distilled off under reduced pressure
  8. customthe resulting residue was purified
  9. washsilica gel column chromatography (elution solvent: ethyl acetate/hexane=30%-70%)

Sources & evidence

ORD record
ord-7123f65876a148adbdc3a8cb18fe0c62
Source dataset
uspto-grants-2011_09
Patent number
US08017610B2

Reaction notes

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