Methanesulfonic Acid → (1S)-1-{(4S)-2-[5-(3-{[(2S)-1-Methoxypropan-2-yl]oxy}-5-[(tripropan-2-ylsilyl)oxy]phenyl)-1H-pyrrol-2-yl]-4,5-dihydro-1,3-oxazol-4-yl}ethanol

HRID 1964691Notes

Reaction equation

HRID 1964691 reaction equation
O[CH2:2][C@H:3]([NH:7][C:8]([C:10]1[NH:11][C:12]([C:15]2[CH:20]=[C:19]([O:21][Si:22]([CH:29]([CH3:31])[CH3:30])([CH:26]([CH3:28])[CH3:27])[CH:23]([CH3:25])[CH3:24])[CH:18]=[C:17]([O:32][C@@H:33]([CH3:37])[CH2:34][O:35][CH3:36])[CH:16]=2)=[CH:13][CH:14]=1)=[O:9])[C@@H:4]([OH:6])[CH3:5].CS(O)(=O)=O.C(N(CC)CC)C.[Cl-].[NH4+]>O1CCCC1>[CH3:36][O:35][CH2:34][C@@H:33]([O:32][C:17]1[CH:16]=[C:15]([C:12]2[NH:11][C:10]([C:8]3[O:9][CH2:2][C@@H:3]([C@@H:4]([OH:6])[CH3:5])[N:7]=3)=[CH:14][CH:13]=2)[CH:20]=[C:19]([O:21][Si:22]([CH:29]([CH3:30])[CH3:31])([CH:26]([CH3:27])[CH3:28])[CH:23]([CH3:24])[CH3:25])[CH:18]=1)[CH3:37]

Participants

6

Reactant 4

HCID 6395Methanesulfonic AcidHCID 8471TriethylamineHCID 25517Ammonium ChlorideHCID 66681176N-[(2S,3S)-1,3-Dihydroxybutan-2-yl]-5-(3-{[(2S)-1-methoxypropan-2-yl]oxy}-5-[(tripropan-2-ylsilyl)oxy]phenyl)-1H-pyrrole-2-carboxamide

Product 1

HCID 66681890(1S)-1-{(4S)-2-[5-(3-{[(2S)-1-Methoxypropan-2-yl]oxy}-5-[(tripropan-2-ylsilyl)oxy]phenyl)-1H-pyrrol-2-yl]-4,5-dihydro-1,3-oxazol-4-yl}ethanolYield 52%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

N-[(2S,3S)-1,3-Dihydroxybutan-2-yl]-5-(3-{[(2S)-1-methoxypropan-2-yl]oxy}-5-[(tripropan-2-ylsilyl)oxy]phenyl)-1H-pyrrole-2-carboxamide (1.76 g, 3.29 mmol) synthesized in Example (112a) was dissolved in tetrahydrofuran (20 mL), and anhydrous methanesulfonic acid (0.54 g, 3.10 mmol) and triethylamine (1.00 mL, 7.17 mmol) were added at −40° C., followed by stirring at the same temperature for 4 hours under nitrogen atmosphere, and then at 50° C. overnight. To the reaction solution, a saturated aqueous ammonium chloride solution (50 mL) was added, and extraction was carried out with methylene chloride (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: methanol/methylene chloride=2%-5%) to afford the desired compound (880 mg, yield 52%) as a white foam.

Workup

  1. customat 50° C.
  2. customovernight
  3. extractionextraction
  4. washThe organic layer was washed with saturated brine
  5. dry with materialsubsequently dried over anhydrous magnesium sulfate
  6. distillationThe solvent was distilled off under reduced pressure
  7. customthe resulting residue was purified
  8. washsilica gel column chromatography (elution solvent: methanol/methylene chloride=2%-5%)

Sources & evidence

ORD record
ord-1440e45b9eb84063905428ef9b2ec7d2
Source dataset
uspto-grants-2013_04
Patent number
US08415359B2

Reaction notes

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