Methanesulfonic Acid → (5R)-2-(5-{3-[(1S)-2-Methoxy-1-methylethoxy]-5-[4-(methylsulfonyl)phenoxy]phenyl}-1H-pyrrol-2-yl)-5-(trifluoromethyl)-4,5-dihydro-1,3-oxazole

HRID 909482Notes

Reaction equation

HRID 909482 reaction equation
[CH3:1][O:2][CH2:3][C@H:4]([CH3:38])[O:5][C:6]1[CH:7]=[C:8]([C:23]2[NH:27][C:26]([C:28]([NH:30][CH2:31][C@H:32](O)[C:33]([F:36])([F:35])[F:34])=[O:29])=[CH:25][CH:24]=2)[CH:9]=[C:10]([O:12][C:13]2[CH:18]=[CH:17][C:16]([S:19]([CH3:22])(=[O:21])=[O:20])=[CH:15][CH:14]=2)[CH:11]=1.C(N(CC)CC)C.CS(O)(=O)=O.C(=O)([O-])O.[Na+]>O1CCCC1>[CH3:1][O:2][CH2:3][C@H:4]([CH3:38])[O:5][C:6]1[CH:7]=[C:8]([C:23]2[NH:27][C:26]([C:28]3[O:29][C@@H:32]([C:33]([F:34])([F:35])[F:36])[CH2:31][N:30]=3)=[CH:25][CH:24]=2)[CH:9]=[C:10]([O:12][C:13]2[CH:18]=[CH:17][C:16]([S:19]([CH3:22])(=[O:20])=[O:21])=[CH:15][CH:14]=2)[CH:11]=1

Participants

6

Reactant 4

HCID 6395Methanesulfonic AcidHCID 8471TriethylamineHCID 516892Sodium BicarbonateHCID 666825025-{3-[(1S)-2-Methoxy-1-methylethoxy]-5-[4-(methylsulfonyl)phenoxy]phenyl}-N-[(2S)-3,3,3-trifluoro-2-hydroxypropyl]-1H-pyrrole-2-carboxamide

Product 1

HCID 58065499(5R)-2-(5-{3-[(1S)-2-Methoxy-1-methylethoxy]-5-[4-(methylsulfonyl)phenoxy]phenyl}-1H-pyrrol-2-yl)-5-(trifluoromethyl)-4,5-dihydro-1,3-oxazoleYield 99.8%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Conditions

Temperature
120 °C

Procedure

5-{3-[(1S)-2-Methoxy-1-methylethoxy]-5-[4-(methylsulfonyl)phenoxy]phenyl}-N-[(2S)-3,3,3-trifluoro-2-hydroxypropyl]-1H-pyrrole-2-carboxamide (339 mg, 0.61 mmol) synthesized in Example (34a) was dissolved in tetrahydrofuran (10 mL), and triethylamine (0.51 mL, 3.66 mmol) and anhydrous methanesulfonic acid (296 mg, 1.71 mmol) were added at 0° C., followed by heating at 120° C. for 30 hours. To the reaction solution, a saturated aqueous sodium hydrogencarbonate solution was added, and extraction was carried out with ethyl acetate (60 mL). After washing with saturated brine, drying was carried out 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=30%-50%) to afford the desired product (328 mg, yield 84%) as a white solid.

Workup

  1. extractionextraction
  2. washAfter washing with saturated brine
  3. customdrying
  4. distillationThe solvent was distilled off under reduced pressure
  5. customthe resulting residue was purified
  6. washsilica gel column chromatography (elution solvent: ethyl acetate/hexane=30%-50%)

Sources & evidence

ORD record
ord-f00d9416791c4064b71008f628db2846
Source dataset
uspto-grants-2011_09
Patent number
US08017610B2

Reaction notes

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