Propargyl bromide → Benzyl 3-oxo-4-(prop-2-yn-1-yl)piperazine-1-carboxylate

HRID 1432918Notes

Reaction equation

HRID 1432918 reaction equation
[H-].[Na+].[CH2:3]([O:10][C:11]([N:13]1[CH2:18][CH2:17][NH:16][C:15](=[O:19])[CH2:14]1)=[O:12])[C:4]1[CH:9]=[CH:8][CH:7]=[CH:6][CH:5]=1.[CH2:20](Br)[C:21]#[CH:22]>C1COCC1.CN(C=O)C>[CH2:3]([O:10][C:11]([N:13]1[CH2:18][CH2:17][N:16]([CH2:22][C:21]#[CH:20])[C:15](=[O:19])[CH2:14]1)=[O:12])[C:4]1[CH:5]=[CH:6][CH:7]=[CH:8][CH:9]=1

Participants

5

Reactant 3

HCID 7842Propargyl bromideHCID 24758Sodium hydrideHCID 736777Benzyl 3-oxopiperazine-1-carboxylate

Product 1

HCID 10891001Benzyl 3-oxo-4-(prop-2-yn-1-yl)piperazine-1-carboxylateYield 100%

Reagents, catalysts & solvents 1

HCID 21974620tetrahydrofuran N,N-dimethylformamideSolvent

Procedure

Sodium hydride (0.82 g, 23.0 mmol, 60% mineral oil dispersion) is added to a solution of 4-benzyloxycarbonylpiperazin-2-one (5.13 g, 21.9 mmol) in THF/DMF (75 mL, 3/1 v/v) at 0° C. The mixture is stirred for 5 minutes, then propargyl bromide (3.7 mL, 41.5 mmol) is added dropwise. The resulting solution is stirred for 1 hour then brought to room temperature and stirred for 2 hours. The reaction is quenched with saturated ammonium chloride solution then diluted with ethyl acetate and washed with water (4×) and brine. The organic layer is dried over MgSO4, filtered and concentrated to dryness. The residue is purified by column chromatography eluting with 5% MeOH/CH2Cl2 to give the product (5.96 g, 21.9 mmol) as a white solid. 1H NMR (CDCl3, 300 MHz) δ7.3 (m, 5H), 5.12 (s, 2H), 4.25 (s,2H), 4.16 (s, 2H), 3.75 (m, 2H), 3.47 (m, 2H), 2.22 (s, 1H).

Workup

  1. stirringThe resulting solution is stirred for 1 hour
  2. customthen brought to room temperature
  3. stirringstirred for 2 hours
  4. customThe reaction is quenched with saturated ammonium chloride solution
  5. additionthen diluted with ethyl acetate
  6. washwashed with water (4×) and brine
  7. dry with materialThe organic layer is dried over MgSO4
  8. filtrationfiltered
  9. concentrationconcentrated to dryness
  10. customThe residue is purified by column chromatography
  11. washeluting with 5% MeOH/CH2Cl2

Sources & evidence

ORD record
ord-fb0abc2308e24f32b7131aa8fb744666
Source dataset
uspto-grants-2009_11
Patent number
US07612075B2

Reaction notes

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