Sodium hydride → (+/-)-4-[3-(Benzhydrylidene-amino)-4-cyano-benzyl]-5-oxo-piperazine-1,3-dicarboxylic acid 1-allyl ester 3-methyl ester

HRID 1433008Notes

Reaction equation

HRID 1433008 reaction equation
[CH3:1][O:2][C:3]([C@H:5]1[NH:10][C:9](=[O:11])[CH2:8][N:7]([C:12]([O:14][CH2:15][CH:16]=[CH2:17])=[O:13])[CH2:6]1)=[O:4].[C:18](=[N:31][C:32]1[CH:39]=[C:38]([CH2:40]Br)[CH:37]=[CH:36][C:33]=1[C:34]#[N:35])([C:25]1[CH:30]=[CH:29][CH:28]=[CH:27][CH:26]=1)[C:19]1[CH:24]=[CH:23][CH:22]=[CH:21][CH:20]=1.[H-].[Na+]>CN(C=O)C>[CH3:1][O:2][C:3]([CH:5]1[N:10]([CH2:40][C:38]2[CH:37]=[CH:36][C:33]([C:34]#[N:35])=[C:32]([N:31]=[C:18]([C:19]3[CH:24]=[CH:23][CH:22]=[CH:21][CH:20]=3)[C:25]3[CH:30]=[CH:29][CH:28]=[CH:27][CH:26]=3)[CH:39]=2)[C:9](=[O:11])[CH2:8][N:7]([C:12]([O:14][CH2:15][CH:16]=[CH2:17])=[O:13])[CH2:6]1)=[O:4]

Participants

5

Reactant 3

HCID 24758Sodium hydrideHCID 179851902-(Benzhydrylideneamino)-4-bromomethylbenzonitrileHCID 53852557(S)-5-oxo-piperazine-1,3-dicarboxylic acid 1-allyl ester 3-methyl ester

Product 1

HCID 54080225(+/-)-4-[3-(Benzhydrylidene-amino)-4-cyano-benzyl]-5-oxo-piperazine-1,3-dicarboxylic acid 1-allyl ester 3-methyl esterYield 39%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

To a solution containing (S)-5-oxo-piperazine-1,3-dicarboxylic acid 1-allyl ester 3-methyl ester (0.43 g, 1.77 mmol), EXAMPLE 56, and 2-(benzhydrylidene-amino)-4-bromomethyl-benzonitrile (0.66 g, 1.77 mmol), EXAMPLE 13, in anhydrous DMF (5 mL) at 0° C. is added 60% NaH (78 mg, 1.95 mmol). After 30 min, the reaction mixture is warmed to ambient temperature and maintained for 6 hours. The reaction mixture is carefully quenched with water and then diluted with water and diethyl ether. The layers are separated and the organic phase is washed twice with water, brine, dried over anhydrous Na2SO4, filtered and concentrated. The crude residue is chromatographed on silica gel (2:1 hexane/ethyl acetate to 1:1 hexane/ethyl acetate) to provide 0.37 g (39%) of the title compound as a glassy solid.

Workup

  1. temperaturemaintained for 6 hours
  2. customThe reaction mixture is carefully quenched with water
  3. additiondiluted with water and diethyl ether
  4. customThe layers are separated
  5. washthe organic phase is washed twice with water, brine
  6. dry with materialdried over anhydrous Na2SO4
  7. filtrationfiltered
  8. concentrationconcentrated
  9. customThe crude residue is chromatographed on silica gel (2:1 hexane/ethyl acetate to 1:1 hexane/ethyl acetate)

Sources & evidence

ORD record
ord-b0d82d1a45174ff7b1b213040136b578
Source dataset
uspto-grants-2009_11
Patent number
US07612075B2

Reaction notes

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