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

HRID 1964680Notes

Reaction equation

HRID 1964680 reaction equation
C[O:2][CH2:3][C@@H:4]([O:6][C:7]1[CH:8]=[C:9]([CH:21]=[C:22]([C:24]2[NH:25][C:26]([C:29]3[O:30][CH2:31][C@@H:32]([CH3:34])[N:33]=3)=[CH:27][CH:28]=2)[CH:23]=1)[O:10][C:11]1[CH:16]=[N:15][C:14]([S:17]([CH3:20])(=[O:19])=[O:18])=[CH:13][N:12]=1)[CH3:5].B(Br)(Br)Br.C(=O)([O-])O.[Na+]>C(Cl)Cl>[CH3:34][C@@H:32]1[CH2:31][O:30][C:29]([C:26]2[NH:25][C:24]([C:22]3[CH:23]=[C:7]([CH:8]=[C:9]([O:10][C:11]4[CH:16]=[N:15][C:14]([S:17]([CH3:20])(=[O:19])=[O:18])=[CH:13][N:12]=4)[CH:21]=3)[O:6][C@@H:4]([CH3:5])[CH2:3][OH:2])=[CH:28][CH:27]=2)=[N:33]1

Participants

5

Reactant 3

HCID 25134Boron tribromideHCID 516892Sodium BicarbonateHCID 666826612-(3-{[(2S)-1-Methoxypropan-2-yl]oxy}-5-{5-[(4R)-4-methyl-4,5-dihydro-1,3-oxazol-2-yl]-1H-pyrrol-2-yl}phenoxy)-5-(methylsulfonyl)pyrazine

Product 1

HCID 44184193(2S)-2-(3-{5-[(4R)-4-Methyl-4,5-dihydro-1,3-oxazol-2-yl]-1H-pyrrol-2-yl]-5-{[5-(methylsulfonyl)pyrazin-2-yl]oxy}phenoxy)propan-1-olYield 74.3%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

2-(3-{[(2S)-1-Methoxypropan-2-yl]oxy}-5-{5-[(4R)-4-methyl-4,5-dihydro-1,3-oxazol-2-yl]-1H-pyrrol-2-yl}phenoxy)-5-(methylsulfonyl)pyrazine (456 mg, 0.94 mmol) synthesized in Example (107e) was dissolved in methylene chloride (5.0 mL), and boron tribromide (1.0 mol/L methylene chloride solution, 1.50 mL, 1.50 mmol) was added dropwise at −78° C., followed by stirring at room temperature for 3 hours under nitrogen atmosphere. To this reaction solution, a saturated aqueous sodium hydrogencarbonate 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=4%-6%) to afford the desired compound (330 mg, yield 74%) 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=4%-6%)

Sources & evidence

ORD record
ord-25b28d073ee74a9a9453db3b9ff1eb95
Source dataset
uspto-grants-2013_04
Patent number
US08415359B2

Reaction notes

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