Benzyl Bromide → Benzyl 4-benzyl-3-oxopiperazine-1-carboxylate

HRID 2109823Notes

Reaction equation

HRID 2109823 reaction equation
[O:1]=[C:2]1[NH:7][CH2:6][CH2:5][N:4]([C:8]([O:10][CH2:11][C:12]2[CH:17]=[CH:16][CH:15]=[CH:14][CH:13]=2)=[O:9])[CH2:3]1.C[Si]([N-][Si](C)(C)C)(C)C.[Li+].C1COCC1.[CH2:33](Br)[C:34]1[CH:39]=[CH:38][CH:37]=[CH:36][CH:35]=1>CN(C=O)C>[CH2:33]([N:7]1[CH2:6][CH2:5][N:4]([C:8]([O:10][CH2:11][C:12]2[CH:17]=[CH:16][CH:15]=[CH:14][CH:13]=2)=[O:9])[CH2:3][C:2]1=[O:1])[C:34]1[CH:39]=[CH:38][CH:37]=[CH:36][CH:35]=1

Participants

6

Reactant 4

HCID 7498Benzyl BromideHCID 8028TetrahydrofuranHCID 736777Benzyl 3-oxopiperazine-1-carboxylateHCID 2733832Lithium Hexamethyldisilazide

Product 1

HCID 59750509Benzyl 4-benzyl-3-oxopiperazine-1-carboxylate

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

To a cold (0° C.) solution of benzyl 3-oxopiperazine-1-carboxylate (4.7 g, 20 mmol) in DMF (75 mL) under an atmosphere of nitrogen, a solution of lithium bis(trimethylsilyl)amide in THF (24 mL, 24 mmol) was added and stirred at the temperature for 30 min. The resultant solution was treated with benzyl bromide (2.9 mL, 24 mmol), and stirred at room temperature overnight. The product mixture was concentrated under vacuum, and the residue partitioned between aqueous HCl and ethyl acetate. The organic extracted was washed with brine, dried over anhydrous magnesium sulfate, filtered, and concentrated under vacuum. The residue was subjected to column chromatography on silica gel eluting with a 50-50 mixture of ethyl acetate and hexane. Collection and concentration of appropriate fractions provided the benzylated product.

Workup

  1. stirringstirred at room temperature overnight
  2. concentrationThe product mixture was concentrated under vacuum
  3. customthe residue partitioned between aqueous HCl and ethyl acetate
  4. extractionThe organic extracted
  5. washwas washed with brine
  6. dry with materialdried over anhydrous magnesium sulfate
  7. filtrationfiltered
  8. concentrationconcentrated under vacuum
  9. additionThe residue was subjected to column chromatography on silica gel eluting with a 50-50 mixture of ethyl acetate and hexane
  10. customCollection and concentration of appropriate fractions
  11. customprovided the benzylated product

Sources & evidence

ORD record
ord-7b1f168dee9d49818ec607bd4c1959e1
Source dataset
uspto-grants-2009_04
Patent number
US07517532B2

Reaction notes

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