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

HRID 909618Notes

Reaction equation

HRID 909618 reaction equation
O[CH2:2][C@H:3]([NH:5][C:6]([C:8]1[NH:9][C:10]([C:13]2[CH:18]=[C:17]([O:19][Si:20]([CH:27]([CH3:29])[CH3:28])([CH:24]([CH3:26])[CH3:25])[CH:21]([CH3:23])[CH3:22])[CH:16]=[C:15]([O:30][C@@H:31]([CH3:35])[CH2:32][O:33][CH3:34])[CH:14]=2)=[CH:11][CH:12]=1)=[O:7])[CH3:4].CS(O)(=O)=O.C(N(CC)CC)C.[Cl-].[NH4+]>O1CCCC1>[CH3:34][O:33][CH2:32][C@@H:31]([O:30][C:15]1[CH:14]=[C:13]([C:10]2[NH:9][C:8]([C:6]3[O:7][CH2:4][C@@H:3]([CH3:2])[N:5]=3)=[CH:12][CH:11]=2)[CH:18]=[C:17]([O:19][Si:20]([CH:24]([CH3:25])[CH3:26])([CH:21]([CH3:22])[CH3:23])[CH:27]([CH3:29])[CH3:28])[CH:16]=1)[CH3:35]

Participants

6

Reactant 4

HCID 6395Methanesulfonic AcidHCID 8471TriethylamineHCID 25517Ammonium ChlorideHCID 66682195N-[(2R)-1-Hydroxypropan-2-yl]-5-(3-{[(2S)-1-methoxypropan-2-yl]oxy}-5-[(tripropan-2-ylsilyl)oxy]phenyl)-1H-pyrrole-2-carboxamide

Product 1

HCID 66681398(4R)-2-[5-(3-{[(2S)-1-Methoxypropan-2-yl]oxy}-5-[(tripropan-2-ylsilyl)oxy]phenyl)-1H-pyrrol-2-yl]-4-methyl-4,5-dihydro-1,3-oxazoleYield 64.5%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Conditions

Temperature
50 °C

Procedure

N-[(2R)-1-Hydroxypropan-2-yl]-5-(3-{[(2S)-1-methoxypropan-2-yl]oxy}-5-[(tripropan-2-ylsilyl)oxy]phenyl)-1H-pyrrole-2-carboxamide (1.95 g, 3.76 mmol) synthesized in Example (107a) was dissolved in tetrahydrofuran (30 mL), and anhydrous methanesulfonic acid (1.25 g, 7.18 mmol) and triethylamine (2.80 mL, 20.09 mmol) were added, followed by stirring at 50° C. for 1 day under nitrogen atmosphere. To the reaction solution, a saturated aqueous ammonium chloride solution (80 mL) was added, and extraction was carried out with methylene chloride (120 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%-80%) to afford the desired compound (1.18 g, yield 64%) as a yellow solid.

Workup

  1. extractionextraction
  2. washThe organic layer was washed with saturated brine
  3. dry with materialsubsequently dried over anhydrous magnesium sulfate
  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=50%-80%)

Sources & evidence

ORD record
ord-06ff2f66fa02461788120523292234f7
Source dataset
uspto-grants-2011_09
Patent number
US08017610B2

Reaction notes

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