Cyanomethylenetributylphosphorane → HCID 69430639, compound

HRID 1269909Notes

Reaction equation

HRID 1269909 reaction equation
[CH3:1][C:2]1[C:10]([OH:11])=[CH:9][CH:8]=[C:7]2[C:3]=1[CH:4]=[N:5][NH:6]2.O[C@@H:13]1[CH2:18][C@H:17]([N:19]2[C:27](=[O:28])[C:26]3[C:21](=[CH:22][CH:23]=[CH:24][CH:25]=3)[C:20]2=[O:29])[C:16]([CH3:31])([CH3:30])[CH2:15][CH2:14]1.C(C=P(CCCC)(CCCC)CCCC)#N>C1(C)C=CC=CC=1>[CH3:30][C:16]1([CH3:31])[CH2:15][CH2:14][C@@H:13]([O:11][C:10]2[C:2]([CH3:1])=[C:3]3[C:7](=[CH:8][CH:9]=2)[NH:6][N:5]=[CH:4]3)[CH2:18][C@@H:17]1[N:19]1[C:27](=[O:28])[C:26]2[C:21](=[CH:22][CH:23]=[CH:24][CH:25]=2)[C:20]1=[O:29]

Participants

5

Reactant 3

HCID 4622928CyanomethylenetributylphosphoraneHCID 229335464-methyl-1H-indazol-5-olHCID 69430046HCID 69430046, compound

Product 1

HCID 69430639HCID 69430639, compoundYield 59.5%

Reagents, catalysts & solvents 1

HCID 1140TolueneSolvent

Conditions

Temperature
100 °C

Procedure

To a solution of the 4-methyl-1H-indazol-5-ol (500 mg, 1.83 mmol) obtained in Example 402 in toluene (8 ml) were added cis-2-(5-hydroxy-2,2-dimethylcyclohexyl)-1H-isoindole-1,3(2H)-dione (400 mg, 1.5 mmol) and cyanomethylenetri-n-butylphosphorane (494 mg, 2.1 mmol) at room temperature, and the resulting mixture was heated to 100° C. After stirring for 7 hours, the reaction solution was concentrated under reduced pressure and the resulting residue was dissolved in chloroform and washed with a 1M-aqueous sodium hydroxide solution. Extraction with chloroform was carried out again and the organic layer was dried over anhydrous magnesium sulfate. The organic layer dried was concentrated under reduced pressure and the resulting residue was purified by a silica gel column chromatography (eluent: hexane/ethyl acetate) to obtain trans-2-{2,2-dimethyl-5-[(4-methyl-1H-indazol-5-yl)oxy]cyclohexyl}-1H-isoindole-1,3(2H)-dione (360 mg, 61%, containing about 10% of cis isomer).

Workup

  1. concentrationthe reaction solution was concentrated under reduced pressure
  2. dissolutionthe resulting residue was dissolved in chloroform
  3. washwashed with a 1M-aqueous sodium hydroxide solution
  4. extractionExtraction with chloroform
  5. dry with materialthe organic layer was dried over anhydrous magnesium sulfate
  6. customThe organic layer dried
  7. concentrationwas concentrated under reduced pressure
  8. customthe resulting residue was purified by a silica gel column chromatography (eluent: hexane/ethyl acetate)

Sources & evidence

ORD record
ord-9c4ebd72cad0493ab093b431bea0edfd
Source dataset
uspto-grants-2007_04
Patent number
US07199147B2

Reaction notes

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