Cyanomethylenetributylphosphorane → trans-2,2-dimethyl-5-[(4-methyl-1H-indazol-5-yl)oxy]cyclohexanecarbonitrile

HRID 1269957Notes

Reaction equation

HRID 1269957 reaction equation
C(C=P(CCCC)(CCCC)CCCC)#N.[OH:17][C@@H:18]1[CH2:23][C@H:22]([C:24]#[N:25])[C:21]([CH3:27])([CH3:26])[CH2:20][CH2:19]1.[CH3:28][C:29]1[C:37](O)=[CH:36][CH:35]=[C:34]2[C:30]=1[CH:31]=[N:32][NH:33]2>C1(C)C=CC=CC=1>[CH3:26][C:21]1([CH3:27])[CH2:20][CH2:19][C@@H:18]([O:17][C:37]2[C:29]([CH3:28])=[C:30]3[C:34](=[CH:35][CH:36]=2)[NH:33][N:32]=[CH:31]3)[CH2:23][C@@H:22]1[C:24]#[N:25]

Participants

5

Reactant 3

HCID 4622928CyanomethylenetributylphosphoraneHCID 229335464-methyl-1H-indazol-5-olHCID 45083033cis-5-Hydroxy-2,2-dimethylcyclohexanecarbonitrile

Product 1

HCID 69429732trans-2,2-dimethyl-5-[(4-methyl-1H-indazol-5-yl)oxy]cyclohexanecarbonitrileYield 46%

Reagents, catalysts & solvents 1

HCID 1140TolueneSolvent2×

Procedure

Under a nitrogen atmosphere, a solution of 90%-cyanomethylenetri-n-butylphosphorane (1.05 g, 4.05 mmol) in toluene (5 ml) was added dropwise to a solution of cis-5-hydroxy-2,2-dimethylcyclohexanecarbonitrile (500 mg, 3.37 mmol) in toluene (12 ml) at room temperature, followed by adding thereto the 4-methyl-1H-indazol-5-ol (507 mg, 3.54 mmol) obtained in Example 402, and the resulting mixture was heated to 100° C. After 4 hours, the reaction solution was concentrated under reduced pressure, and the resulting residue was diluted with chloroform and washed with a 1M-aqueous sodium hydroxide solution. The aqueous layer was re-extracted with chloroform and then 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-dimethyl-5-[(4-methyl-1H-indazol-5-yl)oxy]cyclohexanecarbonitrile (351.1 mg, 46%).

Workup

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

Sources & evidence

ORD record
ord-8f0bdfd186e1481d9b688535018857ce
Source dataset
uspto-grants-2007_04
Patent number
US07199147B2

Reaction notes

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