Sodium Hydroxide → alpha-(3,4-Dimethoxyphenyl)-1,3-dihydro-5,6-dimethoxy-alpha-[(4-methylphenyl)thio]-2H-isoindole-2-heptanenitrile

HRID 1078749Notes

Reaction equation

HRID 1078749 reaction equation
[NH2:1][CH2:2][CH2:3][CH2:4][CH2:5][CH2:6][C:7]([S:20][C:21]1[CH:26]=[CH:25][C:24]([CH3:27])=[CH:23][CH:22]=1)([C:10]1[CH:15]=[CH:14][C:13]([O:16][CH3:17])=[C:12]([O:18][CH3:19])[CH:11]=1)[C:8]#[N:9].Cl[CH2:29][C:30]1[CH:35]=[CH:34][C:33]([O:36][CH3:37])=[C:32]([O:38][CH3:39])[C:31]=1CCl.[OH-].[Na+].[C:44](=O)(O)[O-].[Na+]>[Cl-].C([N+](CCCC)(CCCC)CCCC)CCC.O.C1(C)C=CC=CC=1>[CH3:19][O:18][C:12]1[CH:11]=[C:10]([C:7]([S:20][C:21]2[CH:26]=[CH:25][C:24]([CH3:27])=[CH:23][CH:22]=2)([CH2:6][CH2:5][CH2:4][CH2:3][CH2:2][N:1]2[CH2:29][C:30]3[C:35](=[CH:34][C:33]([O:36][CH3:37])=[C:32]([O:38][CH3:39])[CH:31]=3)[CH2:44]2)[C:8]#[N:9])[CH:15]=[CH:14][C:13]=1[O:16][CH3:17]

Participants

8

Reactant 4

HCID 14798Sodium HydroxideHCID 516892Sodium BicarbonateHCID 10572107alpha-(5-Aminopentyl)-3,4-dimethoxy-alpha-[(4-methylphenyl)thio]benzeneacetonitrileHCID 153389181,2-Bis(chloromethyl)-3,4-dimethoxybenzene

Product 1

HCID 10745170alpha-(3,4-Dimethoxyphenyl)-1,3-dihydro-5,6-dimethoxy-alpha-[(4-methylphenyl)thio]-2H-isoindole-2-heptanenitrile

Reagents, catalysts & solvents 3

HCID 70681Tetrabutylammonium ChlorideCatalystHCID 962WaterSolventHCID 1140TolueneSolvent

Procedure

To a solution of 3.03 g of α-(5-aminopentyl)-3,4-dimethoxy-α-[(4-methylphenyl)thio]benzeneacetonitrile, 1.85 g of 1,2-bis(chloromethyl)-3,4-dimethoxybenzene, 20 mL of toluene, and 0.22 g of tetrabutylammonium chloride, is added water containing 2 g of sodium hydroxide. The mixture is stirred for 48 hours. Upon adjusting the pH of the aqueous layer to pH 9 with solid sodium bicarbonate, the layers are separated and the aqueous layer further extracted with chloroform. After drying the combined organic extracts over sodium sulfate, they are passed through a pad of hydrous magnesium silicate, and concentrated in vacuo to a brown gum. This gum is purified by HPLC using a reverse phase C-18 radial-pak column (6 cm.×30 cm.) with a buffered solvent system (150 mL ammonium hydroxide in water adjusted to a pH 4.00 with acetic acid, then diluted to 7,875 mL with water; 5700 mL of acetonitrile and 1425 mL of methyl alcohol are added). After solvent removal, 0.85 g of the desired product is obtained as a yellow oil.

Workup

  1. customthe layers are separated
  2. extractionthe aqueous layer further extracted with chloroform
  3. dry with materialAfter drying the combined organic extracts over sodium sulfate, they
  4. concentrationconcentrated in vacuo to a brown gum
  5. customThis gum is purified by HPLC
  6. additiondiluted to 7,875 mL with water
  7. addition5700 mL of acetonitrile and 1425 mL of methyl alcohol are added)
  8. customAfter solvent removal

Sources & evidence

ORD record
ord-9f7a674bd4f44e90bc65240c7d8c67c3
Source dataset
uspto-grants-1996_08
Patent number
US05550149

Reaction notes

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