Boron tribromide → (2S)-2-(3-{5-[(4R,5S)-4,5-Dimethyl-4,5-dihydro-1,3-oxazol-2-yl]-1H-pyrrol-2-yl}-5-{[6-(methylsulfonyl)pyridin-3-yl]oxy}phenoxy)propan-1-ol

HRID 1964642Notes

Reaction equation

HRID 1964642 reaction equation
[CH3:1][C@@H:2]1[C@H:6]([CH3:7])[O:5][C:4]([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:18]=[CH:19][C:20]([S:23]([CH3:26])(=[O:25])=[O:24])=[N:21][CH:22]=3)=[CH:10][CH:9]=2)=[N:3]1.B(Br)(Br)Br.C(=O)([O-])O.[Na+]>C(Cl)Cl>[CH3:1][C@@H:2]1[C@H:6]([CH3:7])[O:5][C:4]([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][CH:18]=4)[CH:14]=3)[O:30][C@@H:31]([CH3:35])[CH2:32][OH:33])=[CH:10][CH:9]=2)=[N:3]1

Participants

5

Reactant 3

HCID 25134Boron tribromideHCID 516892Sodium BicarbonateHCID 666813975-(3-{5-[(4R,5S)-4,5-Dimethyl-4,5-dihydro-1,3-oxazol-2-yl]-1H-pyrrol-2-yl}-5-[(1S)-2-methoxy-1-methylethoxy]phenoxy)-2-(methylsulfonyl)pyridine

Product 1

HCID 44184022(2S)-2-(3-{5-[(4R,5S)-4,5-Dimethyl-4,5-dihydro-1,3-oxazol-2-yl]-1H-pyrrol-2-yl}-5-{[6-(methylsulfonyl)pyridin-3-yl]oxy}phenoxy)propan-1-olYield 67%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Conditions

Temperature
-78 °C

Procedure

5-(3-{5-[(4R,5S)-4,5-Dimethyl-4,5-dihydro-1,3-oxazol-2-yl]-1H-pyrrol-2-yl}-5-[(1S)-2-methoxy-1-methylethoxy]phenoxy)-2-(methylsulfonyl)pyridine (0.95 g, 1.96 mmol) synthesized in Example (88c) was dissolved in methylene chloride (20 mL) and cooled to −78° C., and boron tribromide (1.0 mol/L methylene chloride solution, 2.15 mL, 2.15 mmol) was added under nitrogen atmosphere. After the temperature was raised naturally and the solution was stirred at room temperature for 30 minutes, a saturated aqueous sodium hydrogencarbonate solution was added to neutralize the reaction solution, followed by extraction with methylene chloride (80 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: ethyl acetate/hexane=70%-100%) to afford the desired compound (617 mg, 67%) as a white solid.

Workup

  1. temperatureAfter the temperature was raised naturally
  2. extractionfollowed by extraction with methylene chloride (80 mL)
  3. washThe organic layer was washed with saturated brine
  4. dry with materialsubsequently dried over anhydrous magnesium sulfate
  5. distillationThe solvent was distilled off under reduced pressure
  6. customthe resulting residue was purified
  7. washsilica gel column chromatography (elution solvent: ethyl acetate/hexane=70%-100%)

Sources & evidence

ORD record
ord-d258869246e0489ca8aef06989c49e59
Source dataset
uspto-grants-2013_04
Patent number
US08415359B2

Reaction notes

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