Water → N-p-Benzeneacetonitrile menthanecarboxamide

HRID 407529Notes

Reaction equation

HRID 407529 reaction equation
[CH:1]([C@@H:4]1[CH2:9][CH2:8][C@@H:7]([CH3:10])[CH2:6][C@H:5]1[C:11]([NH2:13])=[O:12])([CH3:3])[CH3:2].[C:14]([CH2:16][C:17]1[CH:22]=[CH:21][C:20](I)=[CH:19][CH:18]=1)#[N:15].P([O-])([O-])([O-])=O.[K+].[K+].[K+].O.CNCCNC>[Cu]I.C1(C)C=CC=CC=1>[C:14]([CH2:16][C:17]1[CH:22]=[CH:21][C:20]([NH:13][C:11]([C@@H:5]2[CH2:6][C@H:7]([CH3:10])[CH2:8][CH2:9][C@H:4]2[CH:1]([CH3:2])[CH3:3])=[O:12])=[CH:19][CH:18]=1)#[N:15]

Participants

8

Reactant 5

HCID 962WaterHCID 8070N,N'-DimethylethylenediamineHCID 62657Potassium Phosphate, TribasicHCID 1428664-IodophenylacetonitrileHCID 59253413(1R,2S,5R)-5-Methyl-2-(propan-2-yl)cyclohexane-1-carboxamide

Product 1

HCID 44467796N-p-Benzeneacetonitrile menthanecarboxamide

Reagents, catalysts & solvents 2

HCID 24350Copper(1+) iodide; Copper(I) iodide; Cuprous iodide; Cuprous iodide (CuI)CatalystHCID 1140TolueneSolvent

Conditions

Temperature
100 °C

Procedure

A 250 mL 3-neck flask was fitted with a condenser and a nitrogen inlet was charged with 10.00 g (0.0546 mol) of (1R,2S,5R)-2-isopropyl-5-methylcyclohexanecarboxamide, 0.522 g (0.0027 mol) copper (I) iodide, 13.26 g (0.0546 mol) of 4-(cyanomethyl)phenyl iodide, 23.18 g (0.109 mol) of potassium phosphate. The system was purged with nitrogen and a magnetic stir bar was added. After the addition of 170 mL of toluene, 3.42 g (0.190 mol) of water and 0.964 g (0.0109 mol) of N,N′-dimethylethylene diamine, the mixture was heated to 100° C. and stirred for 21 h under nitrogen. The crude reaction mixture was filtered through 50 g of silica gel (wet with 1:1 ethyl acetate/methylene chloride), and the bed was rinsed three times with 1:1 ethyl acetate/methylene chloride (150+75+75 mL). Concentration of the mixture in vacuo provided N-[4-(cyanomethyl)phenyl]-(1R,2S,5R)-2-isopropyl-5-methylcyclohexanecarboxamide as a thick oil oil which was further purified by flash chromatography on silica gel eluting with mixtures of ethyl acetate and hexanes. The product has the following properties with the structure confirmed by obtaining an X-ray crystal structure of a sample crystallized from hexane/ethyl acetate.

Workup

  1. customA 250 mL 3-neck flask was fitted with a condenser and a nitrogen inlet
  2. customThe system was purged with nitrogen and a magnetic stir bar
  3. additionwas added
  4. customThe crude reaction mixture
  5. filtrationwas filtered through 50 g of silica gel (wet with 1:1 ethyl acetate/methylene chloride)
  6. washthe bed was rinsed three times with 1:1 ethyl acetate/methylene chloride (150+75+75 mL)

Sources & evidence

ORD record
ord-10b88ddd19f54e7a92c349a6791c2a5f
Source dataset
uspto-grants-2014_06
Patent number
US08754259B2

Reaction notes

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