Sodium Hydroxide → HCID 18447091, compound

HRID 1269972Notes

Reaction equation

HRID 1269972 reaction equation
[OH:1][CH:2]1[CH2:7][CH2:6][CH:5]([N:8]2[C:16](=[O:17])[C:15]3[C:10](=[CH:11][CH:12]=[CH:13][CH:14]=3)[C:9]2=[O:18])[CH2:4][CH2:3]1.[CH3:19][O:20][C:21]1[C:29](O)=[CH:28][CH:27]=[C:26]2[C:22]=1[CH:23]=[N:24][NH:25]2.C(C=P(CCCC)(CCCC)CCCC)#N.[OH-].[Na+]>C1(C)C=CC=CC=1.O>[CH3:19][O:20][C:21]1[C:29]([O:1][CH:2]2[CH2:3][CH2:4][CH:5]([N:8]3[C:9](=[O:18])[C:10]4[C:15](=[CH:14][CH:13]=[CH:12][CH:11]=4)[C:16]3=[O:17])[CH2:6][CH2:7]2)=[CH:28][CH:27]=[C:26]2[C:22]=1[CH:23]=[N:24][NH:25]2

Participants

7

Reactant 4

HCID 14798Sodium HydroxideHCID 288726trans-2-(4-Hydroxycyclohexyl)-isoindole-1,3-dioneHCID 4622928CyanomethylenetributylphosphoraneHCID 22933715HCID 22933715, compound

Product 1

HCID 18447091HCID 18447091, compoundYield 66%

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 1140TolueneSolvent

Procedure

Under nitrogen, the 2-(4-hydroxycyclohexyl)-1H-isoindole-1,3(2H)-dione (1.23 g, 5.01 mmol) obtained in Example 385, (b), the 4-methoxy-1H-indazol-5-ol (0.906 g, 5.52 mmol) obtained in Example 469 and 90%-cyanomethylenetri-n-butylphosphorane (161 g, 6.02 mmol) were dissolved in toluene (20 ml), and the resulting solution was heated under reflux for 5 hours. The reaction solution was cooled to room temperature and water and a 1N-aqueous sodium hydroxide solution were added thereto. The resulting solution was separated by the addition of toluene and the desired compound was extracted from the aqueous layer with toluene. The combined toluene layer was washed with a saturated aqueous sodium chloride solution, dried by the addition of anhydrous magnesium sulfate, and then filtered. The solvent was distilled off under reduced pressure and the concentration residue thus obtained was purified by a silica gel column chromatography (eluent: n-hexane/ethyl acetate=2/1, 1/1) to obtain 2-[4-[(4-methoxy-1H-indazol-5-yl)oxy]cyclohexyl]-1H-isoindole-1,3(2H)-dione (1.29 g, yield 66%).

Workup

  1. temperaturethe resulting solution was heated
  2. temperatureunder reflux for 5 hours
  3. customThe resulting solution was separated by the addition of toluene
  4. extractionthe desired compound was extracted from the aqueous layer with toluene
  5. washThe combined toluene layer was washed with a saturated aqueous sodium chloride solution
  6. dry with materialdried by the addition of anhydrous magnesium sulfate
  7. filtrationfiltered
  8. distillationThe solvent was distilled off under reduced pressure
  9. customthe concentration residue thus obtained
  10. customwas purified by a silica gel column chromatography (eluent: n-hexane/ethyl acetate=2/1, 1/1)

Sources & evidence

ORD record
ord-6ed3142e633d4e2ca313f66dfc4ec6e9
Source dataset
uspto-grants-2007_04
Patent number
US07199147B2

Reaction notes

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