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

HRID 1964683Notes

Reaction equation

HRID 1964683 reaction equation
[CH2:1]([C@@H:3]1[CH2:7][O:6][C:5]([C:8]2[NH:12][C:11]([C:13]3[CH:14]=[C:15]([CH:27]=[C:28]([O:30][C@@H:31]([CH3:35])[CH2:32][O:33]C)[CH:29]=3)[O:16][C:17]3[CH:22]=[N:21][C:20]([S:23]([CH3:26])(=[O:25])=[O:24])=[CH:19][N:18]=3)=[CH:10][CH:9]=2)=[N:4]1)[CH3:2].B(Br)(Br)Br.[OH-].[Na+]>C(Cl)Cl>[CH2:1]([C@@H:3]1[CH2:7][O:6][C:5]([C:8]2[NH:12][C:11]([C:13]3[CH:29]=[C:28]([CH:27]=[C:15]([O:16][C:17]4[CH:22]=[N:21][C:20]([S:23]([CH3:26])(=[O:25])=[O:24])=[CH:19][N:18]=4)[CH:14]=3)[O:30][C@@H:31]([CH3:35])[CH2:32][OH:33])=[CH:10][CH:9]=2)=[N:4]1)[CH3:2]

Participants

5

Reactant 3

HCID 14798Sodium HydroxideHCID 25134Boron tribromideHCID 668910952-(3-{5-[(4R)-4-Ethyl-4,5-dihydro-1,3-oxazol-2-yl]-1H-pyrrol-2-yl}-5-{[(2S)-1-methoxypropan-2-yl]oxy}phenoxy)-5-(methylsulfonyl)pyrazine

Product 1

HCID 44184353(2S)-2-(3-{5-[(4R)-4-Ethyl-4,5-dihydro-1,3-oxazol-2-yl]-1H-pyrrol-2-yl]-5-{[5-(methylsulfonyl)pyrazin-2-yl]oxy}phenoxy)propan-1-olYield 80.5%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

2-(3-{5-[(4R)-4-Ethyl-4,5-dihydro-1,3-oxazol-2-yl]-1H-pyrrol-2-yl}-5-{[(2S)-1-methoxypropan-2-yl]oxy}phenoxy)-5-(methylsulfonyl)pyrazine (417 mg, 0.83 mmol) synthesized in Example (108c) was dissolved in methylene chloride (10 mL), and boron tribromide (1.0 mol/L methylene chloride solution, 1.00 mL, 1.00 mmol) was added dropwise at −78° C., followed by stirring at room temperature for 1 hour under nitrogen atmosphere. To this reaction solution, a 1N aqueous sodium hydroxide solution (20 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%-4%) to afford the desired compound (325 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%-4%)

Sources & evidence

ORD record
ord-e00f81b64b47451a810e0996346db31a
Source dataset
uspto-grants-2013_04
Patent number
US08415359B2

Reaction notes

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