Dicyclohexylcarbodiimide → (3S)-3-Methyl-1-(phenylmethyl)-2,5-piperazinedione

HRID 1598441Notes

Reaction equation

HRID 1598441 reaction equation
C1(N=C=NC2CCCCC2)CCCCC1.[C:16]([NH:23][C@H:24]([C:26]([OH:28])=O)[CH3:25])([O:18]C(C)(C)C)=O.[CH2:29]([NH:36][CH2:37]C(OCC)=O)[C:30]1[CH:35]=[CH:34][CH:33]=[CH:32][CH:31]=1>C(Cl)Cl>[CH2:29]([N:36]1[CH2:37][C:16](=[O:18])[NH:23][C@@H:24]([CH3:25])[C:26]1=[O:28])[C:30]1[CH:35]=[CH:34][CH:33]=[CH:32][CH:31]=1

Participants

5

Reactant 3

HCID 10868DicyclohexylcarbodiimideHCID 80908N-Benzylglycine ethyl esterHCID 85082Tert-butoxycarbonylalanine

Product 1

HCID 10513007(3S)-3-Methyl-1-(phenylmethyl)-2,5-piperazinedioneYield 53.9%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent2×

Conditions

Temperature
0 °C

Procedure

The title compound was prepared according to the procedure described by John S. Kiely and Stephen R. Priebe in Organic Preparations and Procedures Int., 22 (6), 761-768 (1990). Thus 100 mL of a stock solution of dicyclohexylcarbodiimide in methylene chloride (0.5M) was added to methylene chloride (250 mL). This solution was cooled to 0° C. under nitrogen and Boc-L-alanine (9.46 g, 50.00 mmol) was added. The resulting slurry was stirred for 5 min, and then ethyl N-benzylglycinate (9.37 mL, 50.00 mmol) was added. The reaction was stirred for 2 h at 0° C., then at 20° C. overnight. The precipitate was removed by filtration, and hydrogen chloride gas bubbled through the methylene chloride solution for 2-4 h, until the reaction was shown to be complete by tlc. The solvent was removed in vacuo, and the residue partitioned between ethyl acetate (150 mL) and saturated sodium bicarbonate solution (42 mL). The organic phase was washed with saturated sodium chloride, dryed over magnesium sulfate, filtered and evaporated. The crude product was recrystallized from toluene to give the title compound as white crystals (5.88 g). NMR (300 MHz, CDCl3) δ 7.30-7.38 (3H, m), 7.22-7.30 (2H, m), 6.94 (1H, br s), 4.59 (2H, s), 4.14 (1H, q, J=7 Hz), 3.84 (2H, s), 1.52 (3H, d, J=7 Hz).

Workup

  1. customThe title compound was prepared
  2. stirringThe reaction was stirred for 2 h at 0° C.
  3. customat 20° C.
  4. customovernight
  5. customThe precipitate was removed by filtration, and hydrogen chloride gas
  6. custombubbled through the methylene chloride solution for 2-4 h, until the reaction
  7. customThe solvent was removed in vacuo
  8. customthe residue partitioned between ethyl acetate (150 mL) and saturated sodium bicarbonate solution (42 mL)
  9. washThe organic phase was washed with saturated sodium chloride
  10. filtrationfiltered
  11. customevaporated
  12. customThe crude product was recrystallized from toluene

Sources & evidence

ORD record
ord-e7d337485065441e953abf07e263aa1f
Source dataset
uspto-grants-1998_04
Patent number
US05736539

Reaction notes

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