Ethyl Acetate → (2S,6R)-4-(4-chloro-quinolin-7-ylmethyl)-2,6-dimethyl-3-oxo-piperazine-1-carboxylic acid benzyl ester

HRID 1432910Notes

Reaction equation

HRID 1432910 reaction equation
[CH2:1]([O:8][C:9]([N:11]1[C@H:16]([CH3:17])[CH2:15][NH:14][C:13](=[O:18])[C@@H:12]1[CH3:19])=[O:10])[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.[H-].[Na+].Br[CH2:23][C:24]1[CH:33]=[C:32]2[C:27]([C:28]([Cl:34])=[CH:29][CH:30]=[N:31]2)=[CH:26][CH:25]=1.C(OCC)(=O)C>C1COCC1.CN(C=O)C>[CH2:1]([O:8][C:9]([N:11]1[C@H:16]([CH3:17])[CH2:15][N:14]([CH2:23][C:24]2[CH:33]=[C:32]3[C:27]([C:28]([Cl:34])=[CH:29][CH:30]=[N:31]3)=[CH:26][CH:25]=2)[C:13](=[O:18])[C@@H:12]1[CH3:19])=[O:10])[C:2]1[CH:3]=[CH:4][CH:5]=[CH:6][CH:7]=1

Participants

7

Reactant 4

HCID 8857Ethyl AcetateHCID 24758Sodium hydrideHCID 217084447-Bromomethyl-4-chloroquinolineHCID 57050377(2S, 6R)-2,6-Dimethyl-3-oxo-piperazine-1-carboxylic acid benzyl ester

Product 1

HCID 57020279(2S,6R)-4-(4-chloro-quinolin-7-ylmethyl)-2,6-dimethyl-3-oxo-piperazine-1-carboxylic acid benzyl esterYield 83%

Reagents, catalysts & solvents 2

HCID 6228DimethylformamideSolventHCID 8028TetrahydrofuranSolvent

Procedure

(2S, 6R)-2,6-Dimethyl-3-oxo-piperazine-1-carboxylic acid benzyl ester (750 mg, 2.86 mmol) is dissolved in 20 mL of THF and 2 mL of DMF. Sodium hydride (60%, 142.6 mg, 6.20 mmol) is added at 0° C., and the reaction is left to stir at room temperature for thirty minutes at which time the 7-bromomethyl-4-chloro-quinoline (952 mg, 3.72 mmol) is added. The reaction is complete after stirring for four hours. Ethyl acetate (200 mL) is added to the mixture, and the reaction is quenched with 3 mL of H2O. The two layers are separated, and ethyl acetate (2×30 mL) is used to extract and dried over magnesium sulfate. The residue after filtration and concentration is chromatographed on silica gel (60% EtOAc/Hexane) to give (2S,6R)-4-(4-chloro-quinolin-7-ylmethyl)-2,6-dimethyl-3-oxo-piperazine-1-carboxylic acid benzyl ester (1.04 g, 83%).

Workup

  1. waitthe reaction is left
  2. additionis added
  3. customthe reaction is quenched with 3 mL of H2O
  4. customThe two layers are separated
  5. extractionto extract
  6. dry with materialdried over magnesium sulfate
  7. filtrationThe residue after filtration and concentration
  8. customis chromatographed on silica gel (60% EtOAc/Hexane)

Sources & evidence

ORD record
ord-d890a8735a2e457aa255c09f5817ef3a
Source dataset
uspto-grants-2009_11
Patent number
US07612075B2

Reaction notes

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