p-Toluenesulfonic acid monohydrate → HCID 68957642, compound

HRID 2378046Notes

Reaction equation

HRID 2378046 reaction equation
[Si:1]([O:8][C:9]1[CH:14]=[CH:13][C:12]([C:15]2[CH:19]([C:20]3[CH:25]=[CH:24][CH:23]=[CH:22][CH:21]=3)[C:18]([C:27]3([C:30]([O:32][CH3:33])=[O:31])[CH2:29][CH2:28]3)(O)[O:17][N:16]=2)=[CH:11][CH:10]=1)([C:4]([CH3:7])([CH3:6])[CH3:5])([CH3:3])[CH3:2].O.C1(C)C=CC(S(O)(=O)=O)=CC=1>C1(C)C=CC=CC=1.C(Cl)(Cl)Cl>[CH3:33][O:32][C:30]([C:27]1([C:18]2[O:17][N:16]=[C:15]([C:12]3[CH:13]=[CH:14][C:9]([O:8][Si:1]([C:4]([CH3:7])([CH3:5])[CH3:6])([CH3:2])[CH3:3])=[CH:10][CH:11]=3)[C:19]=2[C:20]2[CH:25]=[CH:24][CH:23]=[CH:22][CH:21]=2)[CH2:28][CH2:29]1)=[O:31]

Participants

5

Reactant 2

HCID 521998p-Toluenesulfonic acid monohydrateHCID 68957797HCID 68957797, compound2×

Product 1

HCID 68957642HCID 68957642, compound

Reagents, catalysts & solvents 2

HCID 1140TolueneSolventHCID 6212ChloroformSolvent

Conditions

Temperature
80 °C

Procedure

Methyl 1-[3-(4-{[tert-butyl(dimethyl)silyl]oxy}phenyl)-5-hydroxy-4-phenyl-4,5-dihydroisoxazol-5-yl]cyclopropanecarboxylate (Compound C, 42 g) is dissolved in toluene (100 mL) and p-toluenesulfonic acid hydrate (1.7 g) is added with swirling. The mixture is heated over a steam bath until the internal mixture temperature, measured with a digital thermometer, is raised to 80° C. The mixture is then removed from the steam bath and is treated with water (50 mL.) The layers are shaken and separated and the toluene phase is dried over anhydrous magnesium sulfate and is concentrated under reduced pressure to afford an oil that is purified by flash silica gel column chromatography. Elution through a 400 g Analogix silica cartridge with a gradient (100% hexanes to 35% ethyl acetate over 1800 mL, or three column volumes) afforded an oily product. The product is dissolved in chloroform and is reconcentrated under reduced pressure to afford a residue that solidified overnight under high vacuum to the solid product (32 g.)

Workup

  1. temperatureThe mixture is heated over a steam bath until the internal mixture temperature
  2. customThe mixture is then removed from the steam bath
  3. additionis treated with water (50 mL.) The layers
  4. customseparated
  5. dry with materialthe toluene phase is dried over anhydrous magnesium sulfate
  6. concentrationis concentrated under reduced pressure
  7. customto afford an oil that
  8. customis purified by flash silica gel column chromatography
  9. washElution through a 400 g Analogix silica cartridge with a gradient (100% hexanes to 35% ethyl acetate over 1800 mL, or three column volumes)
  10. customafforded an oily product
  11. customto afford a residue that solidified overnight under high vacuum to the solid product (32 g.)

Sources & evidence

ORD record
ord-e0c7d75860b7422f9b41cbb410225a1a
Source dataset
uspto-grants-2008_12
Patent number
US07470715B2

Reaction notes

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