2-Methoxyethanol → 4-[2-(2-Methoxyethoxy)phenyl]-2,2-dimethyl-5-oxopiperazine-1-carboxylic acid t-butyl ester

HRID 1694907Notes

Reaction equation

HRID 1694907 reaction equation
N(C(N1CCCCC1)=O)=NC(N1CCCCC1)=O.[CH3:19][O:20][CH2:21][CH2:22]O.C(P(CCCC)CCCC)CCC.[C:37]([O:41][C:42]([N:44]1[CH2:49][C:48](=[O:50])[N:47]([C:51]2[CH:56]=[CH:55][CH:54]=[CH:53][C:52]=2[OH:57])[CH2:46][C:45]1([CH3:59])[CH3:58])=[O:43])([CH3:40])([CH3:39])[CH3:38]>C1(C)C=CC=CC=1.O>[C:37]([O:41][C:42]([N:44]1[CH2:49][C:48](=[O:50])[N:47]([C:51]2[CH:56]=[CH:55][CH:54]=[CH:53][C:52]=2[O:57][CH2:22][CH2:21][O:20][CH3:19])[CH2:46][C:45]1([CH3:59])[CH3:58])=[O:43])([CH3:40])([CH3:38])[CH3:39]

Participants

7

Reactant 4

HCID 80192-MethoxyethanolHCID 13831TributylphosphineHCID 730421,1'-(Azodicarbonyl)dipiperidineHCID 666456104-(2-Hydroxyphenyl)-2,2-dimethyl-5-oxopiperazine-1-carboxylic acid t-butyl ester

Product 1

HCID 666454244-[2-(2-Methoxyethoxy)phenyl]-2,2-dimethyl-5-oxopiperazine-1-carboxylic acid t-butyl esterYield 86.3%

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 1140TolueneSolvent

Conditions

Temperature
100 °C

Procedure

518 mg of 1,1′-(azodicarbonyl)dipiperidine (2.05 mmol), 156 mg of 2-methoxyethanol (2.05 mmol) and 0.42 ml of tributylphosphine (2.05 mmol) were added to a solution of 400 mg of 4-(2-hydroxyphenyl)-2,2-dimethyl-5-oxopiperazine-1-carboxylic acid t-butyl ester obtained in Example (10d) (1.36 mmol) in toluene (14 ml), and the mixture was stirred at 100° C. for three hours. The reaction mixture was cooled and then water was added, followed by extraction with ethyl acetate. Then, the organic layer was washed with brine and then dried over anhydrous sodium sulfate. After filtration, the solvent was evaporated under reduced pressure, and the residue was purified by silica gel column chromatography (elution solvent:n-hexane/ethyl acetate=1/2) to obtain 444 mg of 4-[2-(2-methoxyethoxy)phenyl]-2,2-dimethyl-5-oxopiperazine-1-carboxylic acid t-butyl ester (yield: 86%).

Workup

  1. temperatureThe reaction mixture was cooled
  2. extractionfollowed by extraction with ethyl acetate
  3. washThen, the organic layer was washed with brine
  4. dry with materialdried over anhydrous sodium sulfate
  5. filtrationAfter filtration
  6. customthe solvent was evaporated under reduced pressure
  7. customthe residue was purified by silica gel column chromatography (elution solvent:n-hexane/ethyl acetate=1/2)

Sources & evidence

ORD record
ord-e05219e15b8441bebfc89f653dfcb2cf
Source dataset
uspto-grants-2012_04
Patent number
US08158790B2

Reaction notes

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