Water → (5R)-2-(5-{3-[(1S)-2-Methoxy-1-methylethoxy]-5-[(triisopropylsilyl)oxy)phenyl]-1H-pyrrol-2-yl)-5{[(triisopropylsilyl)oxy]methyl}-4,5-dihydro-1,3-oxazole

HRID 1964725Notes

Reaction equation

HRID 1964725 reaction equation
O[C@H:2]([CH2:35][O:36][Si:37]([CH:44]([CH3:46])[CH3:45])([CH:41]([CH3:43])[CH3:42])[CH:38]([CH3:40])[CH3:39])[CH2:3][NH:4][C:5]([C:7]1[NH:8][C:9]([C:12]2[CH:17]=[C:16]([O:18][Si:19]([CH:26]([CH3:28])[CH3:27])([CH:23]([CH3:25])[CH3:24])[CH:20]([CH3:22])[CH3:21])[CH:15]=[C:14]([O:29][C@@H:30]([CH3:34])[CH2:31][O:32][CH3:33])[CH:13]=2)=[CH:10][CH:11]=1)=[O:6].CS(O)(=O)=O.C(N(CC)CC)C.O>O1CCCC1>[CH3:33][O:32][CH2:31][C@H:30]([CH3:34])[O:29][C:14]1[CH:13]=[C:12]([C:9]2[NH:8][C:7]([C:5]3[O:6][C@@H:2]([CH2:35][O:36][Si:37]([CH:38]([CH3:40])[CH3:39])([CH:44]([CH3:46])[CH3:45])[CH:41]([CH3:42])[CH3:43])[CH2:3][N:4]=3)=[CH:11][CH:10]=2)[CH:17]=[C:16]([O:18][Si:19]([CH:26]([CH3:27])[CH3:28])([CH:23]([CH3:25])[CH3:24])[CH:20]([CH3:22])[CH3:21])[CH:15]=1

Participants

6

Reactant 4

HCID 962WaterHCID 6395Methanesulfonic AcidHCID 8471TriethylamineHCID 66890970N-{(2S)-2-Hydroxy-3-[(triisopropylsilyl)oxy]propyl}-5-{3-[(1S)-2-methoxy-1-methylethoxy]-5-[(triisopropylsilyl)oxy]phenyl}-1H-pyrrole-2-carboxamide

Product 1

HCID 66682662(5R)-2-(5-{3-[(1S)-2-Methoxy-1-methylethoxy]-5-[(triisopropylsilyl)oxy)phenyl]-1H-pyrrol-2-yl)-5{[(triisopropylsilyl)oxy]methyl}-4,5-dihydro-1,3-oxazoleYield 95%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

N-{(2S)-2-Hydroxy-3-[(triisopropylsilyl)oxy]propyl}-5-{3-[(1S)-2-methoxy-1-methylethoxy]-5-[(triisopropylsilyl)oxy]phenyl}-1H-pyrrole-2-carboxamide (10.54 g, 15.6 mmol) synthesized in Example (125e) was dissolved in tetrahydrofuran (160 mL), and anhydrous methanesulfonic acid (5.51 g, 31.6 mmol) and triethylamine (8.70 mL, 62.4 mmol) were added, followed by stirring at room temperature for 3 hours under nitrogen atmosphere, and subsequently the temperature was raised to 60° C., followed by stirring for 3 hours. To the reaction solution, water (200 mL) was added, and extraction was carried out with ethyl acetate (300 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=5%-30%) to afford the desired compound (9.72 g, yield 95%) as a brown oil.

Workup

  1. temperaturesubsequently the temperature was raised to 60° C.
  2. stirringby stirring for 3 hours
  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: ethyl acetate/hexane=5%-30%)

Sources & evidence

ORD record
ord-3304c50071b74cb686fe09c0f875c6b4
Source dataset
uspto-grants-2013_04
Patent number
US08415359B2

Reaction notes

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