Methanesulfonic Acid → (1R)-1-{(4S)-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}ethanol

HRID 1964658Notes

Reaction equation

HRID 1964658 reaction equation
[OH:1][C@H:2]([CH3:37])[C@@H:3]([NH:6][C:7]([C:9]1[NH:10][C:11]([C:14]2[CH:19]=[C:18]([O:20][C:21]3[CH:22]=[N:23][C:24]([S:27]([CH3:30])(=[O:29])=[O:28])=[CH:25][CH:26]=3)[CH:17]=[C:16]([O:31][C@@H:32]([CH3:36])[CH2:33][O:34][CH3:35])[CH:15]=2)=[CH:12][CH:13]=1)=O)[CH2:4][OH:5].CS(O)(=O)=O.C(N(CC)CC)C.C(=O)([O-])O.[Na+]>O1CCCC1>[CH3:35][O:34][CH2:33][C@H:32]([CH3:36])[O:31][C:16]1[CH:15]=[C:14]([C:11]2[NH:10][C:9]([C:7]3[O:5][CH2:4][C@@H:3]([C@H:2]([OH:1])[CH3:37])[N:6]=3)=[CH:13][CH:12]=2)[CH:19]=[C:18]([O:20][C:21]2[CH:22]=[N:23][C:24]([S:27]([CH3:30])(=[O:28])=[O:29])=[CH:25][CH:26]=2)[CH:17]=1

Participants

6

Reactant 4

HCID 6395Methanesulfonic AcidHCID 8471TriethylamineHCID 516892Sodium BicarbonateHCID 66681687N-[(1S,2R)-2-Hydroxy-1-(hydroxymethyl)propyl]-5-(3-[(1S)-2-methoxy-1-methylethoxy]-5-{[6-(methylsulfonyl)pyridin-3-yl]oxy}phenyl)-1H-pyrrole-2-carboxamide

Product 1

HCID 44184190(1R)-1-{(4S)-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}ethanolYield 55.3%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

N-[(1S,2R)-2-Hydroxy-1-(hydroxymethyl)propyl]-5-(3-[(1S)-2-methoxy-1-methylethoxy]-5-{[6-(methylsulfonyl)pyridin-3-yl]oxy}phenyl)-1H-pyrrole-2-carboxamide (1.42 g, 2.66 mmol) synthesized in Example (95a) was dissolved in tetrahydrofuran (25 mL), and anhydrous methanesulfonic acid (0.72 g, 3.99 mmol) and triethylamine (1.11 mL, 7.98 mmol) were added at 0° C., followed by stirring for 1 hour under nitrogen atmosphere. The temperature was raised naturally, and stirring was carried out at room temperature for 1 hour, followed by stirring at 50° C. for 2 hours. A saturated aqueous sodium hydrogencarbonate solution (30 mL) was added, and the solution was separated with ethyl acetate (50 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=50%-100%) to afford the desired compound (758 mg, yield 55%) as a white solid.

Workup

  1. temperatureThe temperature was raised naturally
  2. stirringstirring
  3. waitwas carried out at room temperature for 1 hour
  4. stirringby stirring at 50° C. for 2 hours
  5. customthe solution was separated with ethyl acetate (50 mL)
  6. washThe organic layer was washed with saturated brine
  7. dry with materialsubsequently dried over anhydrous magnesium sulfate
  8. distillationThe solvent was distilled off under reduced pressure
  9. customthe resulting residue was purified
  10. washsilica gel column chromatography (elution solvent: ethyl acetate/hexane=50%-100%)

Sources & evidence

ORD record
ord-a5eeda1776d548bfa1077de21ceaaef1
Source dataset
uspto-grants-2013_04
Patent number
US08415359B2

Reaction notes

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