Sodium Hydroxide → (2S)-2-[3-(5-{(4S)-4-[(1S)-1-Hydroxyethyl]-4,5-dihydro-1,3-oxazol-2-yl}-1H-pyrrol-2-yl)-5-{[5-(methylsulfonyl)pyrazin-2-yl]oxy}phenoxy]propan-1-ol

HRID 909637Notes

Reaction equation

HRID 909637 reaction equation
C[O:2][CH2:3][C@@H:4]([O:6][C:7]1[CH:8]=[C:9]([C:24]2[NH:28][C:27]([C:29]3[O:30][CH2:31][C@@H:32]([C@@H:34]([OH:36])[CH3:35])[N:33]=3)=[CH:26][CH:25]=2)[CH:10]=[C:11]([O:13][C:14]2[CH:19]=[N:18][C:17]([S:20]([CH3:23])(=[O:22])=[O:21])=[CH:16][N:15]=2)[CH:12]=1)[CH3:5].B(Br)(Br)Br.[OH-].[Na+]>C(Cl)Cl>[OH:36][C@H:34]([C@@H:32]1[CH2:31][O:30][C:29]([C:27]2[NH:28][C:24]([C:9]3[CH:8]=[C:7]([CH:12]=[C:11]([O:13][C:14]4[CH:19]=[N:18][C:17]([S:20]([CH3:23])(=[O:22])=[O:21])=[CH:16][N:15]=4)[CH:10]=3)[O:6][C@@H:4]([CH3:5])[CH2:3][OH:2])=[CH:25][CH:26]=2)=[N:33]1)[CH3:35]

Participants

5

Reactant 3

HCID 14798Sodium HydroxideHCID 25134Boron tribromideHCID 51042424(1S)-1-{(4S)-2-[5-(3-{[(2S)-1-Methoxypropan-2-yl]oxy}-5-{[5-(methylsulfonyl)pyrazin-2-yl]oxy}phenyl)-1H-pyrrol-2-yl]-4,5-dihydro-1,3-oxazol-4-yl}ethanol

Product 1

HCID 58065496(2S)-2-[3-(5-{(4S)-4-[(1S)-1-Hydroxyethyl]-4,5-dihydro-1,3-oxazol-2-yl}-1H-pyrrol-2-yl)-5-{[5-(methylsulfonyl)pyrazin-2-yl]oxy}phenoxy]propan-1-olYield 80.1%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

(1S)-1-{(4S)-2-[5-(3-{[(2S)-1-Methoxypropan-2-yl]oxy}-5-{[5-(methylsulfonyl)pyrazin-2-yl]oxy}phenyl)-1H-pyrrol-2-yl]-4,5-dihydro-1,3-oxazol-4-yl}ethanol (204 mg, 0.395 mmol) synthesized in Example (112d) was dissolved in methylene chloride (5.0 mL), and boron tribromide (1.0 mol/L methylene chloride solution, 0.80 mL, 0.80 mmol) was added dropwise at −78° C., followed by stirring at room temperature for 1.5 hours under nitrogen atmosphere. To this reaction solution, a 1N aqueous sodium hydroxide solution (10 mL) was added, and extraction was carried out with methylene chloride (20 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=3%-5%) to afford the desired compound (159 mg, yield 80%) 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=3%-5%)

Sources & evidence

ORD record
ord-9a5c982646514e2c92e94affdbbbb0c0
Source dataset
uspto-grants-2011_09
Patent number
US08017610B2

Reaction notes

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