1,4-dibenzyl-2,5-piperazinedione → HCID 67051729, compound

HRID 1809032Notes

Reaction equation

HRID 1809032 reaction equation
[C:1]1([CH2:7][N:8]2[CH2:13][C:12](=[O:14])[N:11]([CH2:15][C:16]3[CH:21]=[CH:20][CH:19]=[CH:18][CH:17]=3)[CH2:10][C:9]2=[O:22])[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=1.C([N-]C(C)C)(C)C.[Li+].[O:31]=[C:32]1[CH2:35][N:34]([C:36]([O:38][C:39]([CH3:42])([CH3:41])[CH3:40])=[O:37])[CH2:33]1>C1COCC1>[O:14]=[C:12]1[N:11]([CH2:15][C:16]2[CH:21]=[CH:20][CH:19]=[CH:18][CH:17]=2)[CH2:10][C:9](=[O:22])[N:8]([CH2:7][C:1]2[CH:2]=[CH:3][CH:4]=[CH:5][CH:6]=2)[CH:13]1[C:32]1([OH:31])[CH2:33][N:34]([C:36]([O:38][C:39]([CH3:41])([CH3:40])[CH3:42])=[O:37])[CH2:35]1

Participants

5

Reactant 3

HCID 6821071,4-dibenzyl-2,5-piperazinedioneHCID 15194043-Oxo-azetidine-1-carboxylic acid tert-butyl esterHCID 2724682Lithium diisopropylamide

Product 1

HCID 67051729HCID 67051729, compoundYield 50%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent2×

Conditions

Temperature
-78 °C

Procedure

To a solution of commercially available 1,4-bis(phenylmethyl)piperazine-2,5-dione (2.0 g, 6.8 mmol) in dry THF (50 mL) at −78° C. was added lithium diisopropylamide (2.0 M solution in heptane/THF/ethylbenzene, 3.4 mL, 6.8 mmol). The resulting reddish brown suspension was stirred for 23 min at −78° C., and then a solution of 1,1-dimethylethyl 3-oxoazetidine-1-carboxylate (770 mg, 4.5 mmol) in THF (10 mL) was added over 30 min by syringe pump. The mixture became a bright yellow solution as it was allowed to warm to room temperature over 3 hours. The mixture was quenched with saturated aqueous ammonium chloride. Water was added to dissolve precipitated salts, and the resulting mixture was extracted twice with ethyl acetate. The combined organic extracts were dried over magnesium sulfate, filtered, and concentrated. The residue was purified by column chromatography (60% ethyl acetate: 40% hexanes) to provide 1,1-dimethylethyl 3-[3,6-dioxo-1,4-bis(phenylmethyl)piperazin-2-yl]-3-hydroxyazetidine-carboxylate as a colorless foam (1.04 g, 2.23 mmol, 50% yield). 1H NMR. (400 MHz, CDCl3): 7.39-7.29 (m, 7H), 7.23-7.19 (m, 3H), 5.34 (d, 1H), 4.82 (d, 1H), 4.58 (d, 1H), 4.37 (d, 1H), 4.37 (d, 1H), 4.22 (d, 1H), 4.15 (s, 1H), 4.08 (d, 1H), 3.97 (d, 1H), 3.75 (d, 1H), 3.74 (d, 1H), 3.67 (d, 1H), 3.64 (br s, 1H), 1.43 (s, 9H).

Workup

  1. temperatureto warm to room temperature over 3 hours
  2. customThe mixture was quenched with saturated aqueous ammonium chloride
  3. additionWater was added
  4. dissolutionto dissolve
  5. customprecipitated salts
  6. extractionthe resulting mixture was extracted twice with ethyl acetate
  7. dry with materialThe combined organic extracts were dried over magnesium sulfate
  8. filtrationfiltered
  9. concentrationconcentrated
  10. customThe residue was purified by column chromatography (60% ethyl acetate: 40% hexanes)

Sources & evidence

ORD record
ord-13975f9a4cb943f78a2613dabe3abba7
Source dataset
uspto-grants-2013_01
Patent number
US08362002B2

Reaction notes

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