Water → HCID 87539088, compound

HRID 1443233Notes

Reaction equation

HRID 1443233 reaction equation
Cl[C:2]1[CH:11]=[CH:10][C:9]2[CH:8]([NH:12][C:13]3[CH:14]=[N:15][CH:16]=[CH:17][CH:18]=3)[C:7]([C:20]([F:23])([F:22])[F:21])([OH:19])[CH2:6][C:5]([CH3:25])([CH3:24])[C:4]=2[C:3]=1[OH:26].[C-:27]#[N:28].[Na+].O>CN1CCCC1=O.C(OCC)(=O)C.[Ni](Br)Br>[OH:26][C:3]1[C:4]2[C:5]([CH3:25])([CH3:24])[CH2:6][C:7]([OH:19])([C:20]([F:23])([F:22])[F:21])[CH:8]([NH:12][C:13]3[CH:14]=[N:15][CH:16]=[CH:17][CH:18]=3)[C:9]=2[CH:10]=[CH:11][C:2]=1[C:27]#[N:28]

Participants

7

Reactant 3

HCID 962WaterHCID 8929Sodium CyanideHCID 87538493HCID 87538493, compound

Product 1

HCID 87539088HCID 87539088, compoundYield 19.3%

Reagents, catalysts & solvents 3

HCID 278492Nickel(II) bromideCatalystHCID 8857Ethyl AcetateSolventHCID 13387N-methyl-2-pyrrolidoneSolvent

Procedure

50 mg of the 2-chloro-8,8-dimethyl-5-(pyridin-3-ylamino)-6-(trifluoromethyl)-5,6,7,8-tetrahydronaphthalene-1,6-diol that is described in Example 159 is dissolved in 0.12 ml of 1-methyl-2-pyrrolidinone and mixed with 12.6 mg (0.258 mmol) of sodium cyanide and 28.2 mg (0.129 mmol) of nickel(II) bromide. The reaction mixture is brought to reaction in a microwave (200° C., 20 bar) as described in the literature (J. Org. Chem. 68, 9122 (2003)). After cooling, the reaction mixture is diluted with ethyl acetate, and then a small amount of water is added. The mixture is filtered on Extrelute (mobile solvent: ethyl acetate). The solvent is spun off, and the residue is chromatographed on silica gel (mobile solvent: methanol/dichloromethane). 9.4 mg (19.2%) of the desired nitrile is isolated.

Workup

  1. customThe reaction mixture is brought to reaction in a microwave (200° C., 20 bar)
  2. temperatureAfter cooling
  3. filtrationThe mixture is filtered on Extrelute (mobile solvent: ethyl acetate)
  4. customthe residue is chromatographed on silica gel (mobile solvent: methanol/dichloromethane)

Sources & evidence

ORD record
ord-8945d06bfb92413bb779c95402487415
Source dataset
uspto-grants-2010_02
Patent number
US07659297B2

Reaction notes

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