Thionyl Chloride → 1,3-Dibenzylpiperazine-2,5-dione

HRID 1363859Notes

Reaction equation

HRID 1363859 reaction equation
COC(=O)[C@H:4]([CH2:24][C:25]1[CH:30]=[CH:29][CH:28]=[CH:27][CH:26]=1)[NH:5][C:6](=[O:23])[CH2:7][N:8]([C:16](OC(C)(C)C)=[O:17])[CH2:9][C:10]1[CH:15]=[CH:14][CH:13]=[CH:12][CH:11]=1.S(Cl)(Cl)=O>CO>[CH2:9]([N:8]1[CH2:7][C:6](=[O:23])[NH:5][CH:4]([CH2:24][C:25]2[CH:30]=[CH:29][CH:28]=[CH:27][CH:26]=2)[C:16]1=[O:17])[C:10]1[CH:15]=[CH:14][CH:13]=[CH:12][CH:11]=1

Participants

4

Reactant 2

HCID 24386Thionyl ChlorideHCID 66941116(+/-)-N-tert-Butoxycarbonyl-N-benzylglycyl-phenylalanine Methyl Ester

Product 1

HCID 133505981,3-Dibenzylpiperazine-2,5-dioneYield 92%

Reagents, catalysts & solvents 1

HCID 887MethanolSolvent

Procedure

To a 0° C. solution of dipeptide 5 (2.18 g, 5.11 mmol) in methanol (30 mL) was slowly added excess thionyl chloride (1.9 mL). The solution stirred at ambient temperature for 2.5 h. The solvent was evaporated and the residue was triturated with ˜30 mL of ether, producing a white solid that was collected by filtration. The solid was dissolved in methanol (40 mL) and treated with ammonium hydroxide (29%, 10 mL) and then stirred for 18 h followed by concentration. The solid residue was partitioned between saturated NaHCO3 (40 mL), water (20 mL) and CHCl3:isopropyl alcohol, 4:1 (40 mL). The organic phase was separated and the aqueous phase extracted with CHCl3:isopropyl alcohol, 4:1 (3×40 mL). The combined organic phases were dried (K2CO3) and concentrated to afford 6 as a white solid (1.382 g, 92% yield). 1H NMR (400 MHz, CDCl3): δ 2.99 (d, part of AB pattern, J=17.6 Hz, 1H), 3.17 (m, AB pattern, 2H), 3.52 (d, part of AB pattern, J=17.6 Hz, 1H), 4.35 (m, 1H), 4.48 (m, AB pattern, J=14.7 Hz, 1H), 6.39 (bs, NH, 1H), 7.13-7.35 (m, 10H, overlapped with CDCl3); 13C NMR (100 MHz, CDCl3): δ 40.5, 48.2, 49.6, 56.4, 127.4, 128.1, 128.59, 128.63, 128.8, 130.0, 134.65, 134.68, 165.2, 166.3.

Workup

  1. customTo a 0° C.
  2. customThe solvent was evaporated
  3. customthe residue was triturated with ˜30 mL of ether
  4. customproducing a white solid
  5. filtrationthat was collected by filtration
  6. dissolutionThe solid was dissolved in methanol (40 mL)
  7. additiontreated with ammonium hydroxide (29%, 10 mL)
  8. stirringstirred for 18 h
  9. concentrationfollowed by concentration
  10. customThe solid residue was partitioned between saturated NaHCO3 (40 mL), water (20 mL) and CHCl3
  11. customThe organic phase was separated
  12. extractionthe aqueous phase extracted with CHCl3
  13. dry with materialThe combined organic phases were dried (K2CO3)
  14. concentrationconcentrated

Sources & evidence

ORD record
ord-5972ad7b37614b44b1f808b847188c9f
Source dataset
uspto-grants-2011_02
Patent number
US07887784B2

Reaction notes

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