N,N'-Dimethylethylenediamine → 1-(4-Amino-2-chlorophenyl)-3-({[tert-butyl(diphenyl)silyl]oxy}methyl)piperidin-2-one

HRID 218533

Reaction equation

HRID 218533 reaction equation
[Cl:1][C:2]1[CH:3]=[C:4]([CH:6]=[CH:7][C:8]=1I)[NH2:5].[Si:10]([O:27][CH2:28][CH:29]1[CH2:34][CH2:33][CH2:32][NH:31][C:30]1=[O:35])([C:23]([CH3:26])([CH3:25])[CH3:24])([C:17]1[CH:22]=[CH:21][CH:20]=[CH:19][CH:18]=1)[C:11]1[CH:16]=[CH:15][CH:14]=[CH:13][CH:12]=1.P([O-])([O-])([O-])=O.[K+].[K+].[K+].CNCCNC>O1CCOCC1.[Cu]I>[NH2:5][C:4]1[CH:6]=[CH:7][C:8]([N:31]2[CH2:32][CH2:33][CH2:34][CH:29]([CH2:28][O:27][Si:10]([C:23]([CH3:25])([CH3:24])[CH3:26])([C:11]3[CH:16]=[CH:15][CH:14]=[CH:13][CH:12]=3)[C:17]3[CH:22]=[CH:21][CH:20]=[CH:19][CH:18]=3)[C:30]2=[O:35])=[C:2]([Cl:1])[CH:3]=1

Participants

7

Reactant 4

HCID 8070N,N'-DimethylethylenediamineHCID 62657Potassium Phosphate, TribasicHCID 2829263-Chloro-4-iodoanilineHCID 59410781HCID 59410781, compound

Product 1

HCID 595867621-(4-Amino-2-chlorophenyl)-3-({[tert-butyl(diphenyl)silyl]oxy}methyl)piperidin-2-one

Reagents, catalysts & solvents 2

HCID 24350Copper(1+) iodide; Copper(I) iodide; Cuprous iodide; Cuprous iodide (CuI)CatalystHCID 312751,4-DioxaneSolvent

Procedure

2.75 g (10.8 mmol) of 3-chloro-4-iodoaniline are dissolved in 20 ml of anhydrous dioxane and admixed successively with 4.98 g (13.5 mmol) of the compound from example 92A, 103 mg (0542 mmol) of copper(I) iodide, 4.61 g (21.7 mmol) of potassium phosphate and 116 μl (1.085 mmol) of N,N′-dimethylethylenediamine. The reflux apparatus is inertized by repeated application of a gentle vacuum and flushing with argon. The reaction mixture is heated to reflux for 15 hours. After this time, it is allowed to cool to RT. It is admixed with water and extracted with ethyl acetate. The organic extract is washed successively with water and saturated sodium chloride solution. Then it is dried over anhydrous magnesium sulfate and filtered, and the filtrate is freed of the solvent under reduced pressure. The crude product thus obtained is first purified by suction filtration through silica gel with 20:1→1:4 cyclohexane/ethyl acetate as the eluent. This affords 3.12 g of a still-contaminated product which is purified further by means of preparative HPLC with an acetonitrile/water mixture. This affords 0.71 g (13% of theory) of the title compound.

Workup

  1. customflushing with argon
  2. temperatureThe reaction mixture is heated
  3. temperatureto reflux for 15 hours
  4. extractionextracted with ethyl acetate
  5. extractionThe organic extract
  6. washis washed successively with water and saturated sodium chloride solution
  7. dry with materialThen it is dried over anhydrous magnesium sulfate
  8. filtrationfiltered

Sources & evidence

ORD record
ord-b01ea25bb9c34053a1d02ec92d02d28a
Source dataset
uspto-grants-2012_06
Patent number
US08198267B2

Linked notes

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