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

HRID 909579Notes

Reaction equation

HRID 909579 reaction equation
C[O:2][CH2:3][C@H:4]([CH3:35])[O:5][C:6]1[CH:7]=[C:8]([C:23]2[NH:27][C:26]([C:28]3[O:29][CH2:30][C@@H:31]([CH2:33][OH:34])[N:32]=3)=[CH:25][CH:24]=2)[CH:9]=[C:10]([O:12][C:13]2[CH:14]=[N:15][C:16]([S:19]([CH3:22])(=[O:21])=[O:20])=[CH:17][CH:18]=2)[CH:11]=1.B(Br)(Br)Br.C(=O)([O-])O.[Na+]>C(Cl)Cl>[OH:34][CH2:33][C@@H:31]1[CH2:30][O:29][C:28]([C:26]2[NH:27][C:23]([C:8]3[CH:7]=[C:6]([CH:11]=[C:10]([O:12][C:13]4[CH:14]=[N:15][C:16]([S:19]([CH3:22])(=[O:21])=[O:20])=[CH:17][CH:18]=4)[CH:9]=3)[O:5][C@@H:4]([CH3:35])[CH2:3][OH:2])=[CH:24][CH:25]=2)=[N:32]1

Participants

5

Reactant 3

HCID 25134Boron tribromideHCID 516892Sodium BicarbonateHCID 44184021{(4R)-2-[5-(3-[(1S)-2-Methoxy-1-methylethoxy]-5-{[6-(methylsulfonyl)pyridin-3-yl]oxy}phenyl)-1H-pyrrol-2-yl]-4,5-dihydro-1,3-oxazol-4-yl}methanol

Product 1

HCID 58065525(2S)-2-(3-{5-[(4R)-4-(Hydroxymethyl)-4,5-dihydro-1,3-oxazol-2-yl]-1H-pyrrol-2-yl}-5-{[6-(methylsulfonyl)pyridin-3-yl]oxy}phenoxy)propan-1-olYield 74%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Conditions

Temperature
-78 °C

Procedure

{(4R)-2-[5-(3-[(1S)-2-Methoxy-1-methylethoxy]-5-{[6-(methylsulfonyl)pyridin-3-yl]oxy}phenyl)-1H-pyrrol-2-yl]-4,5-dihydro-1,3-oxazol-4-yl}methanol (200 mg, 0.40 mmol) synthesized in Example (86c) was dissolved in methylene chloride (5 mL), followed by cooling to −78° C., and boron tribromide (1.0 mol/L methylene chloride solution, 0.80 mL, 0.80 mmol) was added under nitrogen atmosphere. After the temperature was raised naturally and stirring was carried out 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 1N aqueous sodium hydroxide solution and 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%-4%) to afford the desired compound (143 mg, 74%) 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 1N aqueous sodium hydroxide solution and 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: methanol/methylene chloride=0%-4%)

Sources & evidence

ORD record
ord-e256540dc5204df5970c116a81bdf655
Source dataset
uspto-grants-2011_09
Patent number
US08017610B2

Reaction notes

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