Water → {(5R)-2-[5-(3-[(1S)-2-Methoxy-1-methylethoxy]-5-{[5-(methylsulfonyl)pyrazin-2-yl]oxy}phenyl)-1H-pyrrol-2-yl]-4,5-dihydro-1,3-oxazol-5-yl}methanol

HRID 1964666Notes

Reaction equation

HRID 1964666 reaction equation
[CH3:1][O:2][CH2:3][C@H:4]([CH3:45])[O:5][C:6]1[CH:7]=[C:8]([CH:20]=[C:21]([C:23]2[NH:24][C:25]([C:28]3[O:29][C@@H:30]([CH2:33][O:34][Si](C(C)C)(C(C)C)C(C)C)[CH2:31][N:32]=3)=[CH:26][CH:27]=2)[CH:22]=1)[O:9][C:10]1[CH:15]=[N:14][C:13]([S:16]([CH3:19])(=[O:18])=[O:17])=[CH:12][N:11]=1.[F-].C([N+](CCCC)(CCCC)CCCC)CCC.O>O1CCCC1>[CH3:1][O:2][CH2:3][C@H:4]([CH3:45])[O:5][C:6]1[CH:22]=[C:21]([C:23]2[NH:24][C:25]([C:28]3[O:29][C@@H:30]([CH2:33][OH:34])[CH2:31][N:32]=3)=[CH:26][CH:27]=2)[CH:20]=[C:8]([O:9][C:10]2[CH:15]=[N:14][C:13]([S:16]([CH3:19])(=[O:18])=[O:17])=[CH:12][N:11]=2)[CH:7]=1

Participants

5

Reactant 3

HCID 962WaterHCID 2724141Tetrabutylammonium FluorideHCID 66681066HCID 66681066, compound

Product 1

HCID 58065484{(5R)-2-[5-(3-[(1S)-2-Methoxy-1-methylethoxy]-5-{[5-(methylsulfonyl)pyrazin-2-yl]oxy}phenyl)-1H-pyrrol-2-yl]-4,5-dihydro-1,3-oxazol-5-yl}methanolYield 35%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

2-(3-[(1S)-2-Methoxy-1-methylethoxy]-5-{5-[(5R)-5-{[(triisopropylsilyl)oxy]methyl}-4,5-dihydro-1,3-oxazol-2-yl]-1H-pyrrol-2-yl}phenoxy)-5-(methylsulfonyl)pyrazine (496 mg, 0.82 mmol) synthesized in Example (101c) was dissolved in tetrahydrofuran (20 mL), and tetrabutylammonium fluoride (1.0 mol/L tetrahydrofuran solution, 0.82 mL, 0.82 mmol) was added, followed by stirring for 2 hours under nitrogen atmosphere. To the reaction solution, water (40 mL) was added, and extraction was carried out twice with ethyl acetate (40 mL). The organic layer was washed with saturated brine, and subsequently 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: methanol/methylene chloride=0%-5%) to afford the desired compound (133 mg, yield 35%) as a white solid.

Workup

  1. extractionextraction
  2. washThe organic layer was washed with saturated brine
  3. dry with materialsubsequently dried over anhydrous magnesium sulfate
  4. distillationThe solvent was distilled off under reduced pressure
  5. customthe resulting residue was purified
  6. washsilica gel column chromatography (elution solvent: methanol/methylene chloride=0%-5%)

Sources & evidence

ORD record
ord-dba4fded60164198b7f44bd910be9f98
Source dataset
uspto-grants-2013_04
Patent number
US08415359B2

Reaction notes

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