Water → {(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

HRID 1964639Notes

Reaction equation

HRID 1964639 reaction equation
[CH3:1][O:2][CH2:3][C@H:4]([CH3:37])[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]([C:33](OC)=[O: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.[H-].[Al+3].[Li+].[H-].[H-].[H-].O.[OH-].[Na+]>O1CCCC1.C(OCC)(=O)C>[CH3:1][O:2][CH2:3][C@H:4]([CH3:37])[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:20])=[O:21])=[CH:17][CH:18]=2)[CH:11]=1

Participants

7

Reactant 4

HCID 962Water2×HCID 14798Sodium HydroxideHCID 21226445Aluminium lithium hydrideHCID 66681625Methyl (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-oxazole-4-carboxylate

Product 1

HCID 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}methanolYield 69.1%

Reagents, catalysts & solvents 2

HCID 8028TetrahydrofuranSolventHCID 8857Ethyl AcetateSolvent

Procedure

Methyl (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-oxazole-4-carboxylate (1.76 g, 3.32 mmol) synthesized in Example (86b) was dissolved in tetrahydrofuran (30 mL), and lithium aluminum hydride (0.25 g, 6.65 mmol) was added at 0° C. After stirring for 30 minutes under nitrogen atmosphere, water (0.25 mL), a 5N aqueous sodium hydroxide solution (0.25 mL) and water (0.75 mL) were added in this order, and stirring was carried out for 10 minutes. Ethyl acetate (100 mL) was added followed by stirring for 5 minutes, and subsequently 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: methanol/methylene chloride=0%-5%) to afford the desired compound (1.15 g, 69%) as a white powder.

Workup

  1. stirringstirring
  2. waitwas carried out for 10 minutes
  3. stirringby stirring for 5 minutes
  4. customsubsequently drying
  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%-5%)

Sources & evidence

ORD record
ord-29869b5f949344a28c1c8d9318db6795
Source dataset
uspto-grants-2013_04
Patent number
US08415359B2

Reaction notes

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