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

HRID 909593Notes

Reaction equation

HRID 909593 reaction equation
C[O:2][CH2:3][C@H:4]([CH3:36])[O:5][C:6]1[CH:7]=[C:8]([C:23]2[NH:27][C:26]([C:28]3[O:29][C@@H:30]([CH3:35])[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[C@H:30]([CH3:35])[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]([CH3:36])[CH2:3][OH:2])=[CH:24][CH:25]=2)=[N:32]1

Participants

5

Reactant 3

HCID 25134Boron tribromideHCID 516892Sodium BicarbonateHCID 44184024{(4R,5S)-2-[5-(3-[(1S)-2-Methoxy-1-methylethoxy]-5-{[6-(methylsulfonyl)pyridin-3-yl]oxy}phenyl)-1H-pyrrol-2-yl]-5-methyl-4,5-dihydro-1,3-oxazol-4-yl}methanol

Product 1

HCID 58065504(2S)-2-(3-{5-[(4R,5S)-4-(Hydroxymethyl)-5-methyl-4,5-dihydro-1,3-oxazol-2-yl]-1H-pyrrol-2-yl}-5-{[6-(methylsulfonyl)pyridin-3-yl]oxy}phenoxy)propan-1-olYield 82%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

{(4R,5S)-2-[5-(3-[(1S)-2-Methoxy-1-methylethoxy]-5-{[6-(methylsulfonyl)pyridin-3-yl]oxy}phenyl)-1H-pyrrol-2-yl]-5-methyl-4,5-dihydro-1,3-oxazol-4-yl}methanol (178 mg, 0.35 mmol) synthesized in Example (91d) was dissolved in methylene chloride (5 mL), and boron tribromide (1.0 mol/L methylene chloride solution, 0.70 mL, 0.70 mmol) was added at −78° C., and subsequently the temperature was brought back to room temperature and stirring was carried out for 45 minutes. To the reaction solution, a saturated aqueous sodium hydrogencarbonate solution was added, and extraction was carried out with methylene chloride. The organic layer was washed with saturated brine, and subsequently dried over sodium 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 (142 mg, yield 82%) as a white solid.

Workup

  1. customwas brought back to room temperature
  2. extractionextraction
  3. washThe organic layer was washed with saturated brine
  4. dry with materialsubsequently dried over sodium 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-64fc251208734444bc4f0ca46fed95b5
Source dataset
uspto-grants-2011_09
Patent number
US08017610B2

Reaction notes

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