Hydrochloric Acid → HCID 67051639, compound

HRID 1672971Notes

Reaction equation

HRID 1672971 reaction equation
[O:1]=[C:2]1[N:7]([CH2:8][C:9]2[CH:14]=[CH:13][CH:12]=[CH:11][CH:10]=2)[CH2:6][C:5](=[O:15])[N:4]([CH2:16][C:17]2[CH:22]=[CH:21][CH:20]=[CH:19][CH:18]=2)[CH:3]1[C:23]1([OH:34])[CH2:26][N:25](C(OC(C)(C)C)=O)[CH2:24]1.Cl.O1CCOCC1>CO>[OH:34][C:23]1([CH:3]2[N:4]([CH2:16][C:17]3[CH:22]=[CH:21][CH:20]=[CH:19][CH:18]=3)[C:5](=[O:15])[CH2:6][N:7]([CH2:8][C:9]3[CH:14]=[CH:13][CH:12]=[CH:11][CH:10]=3)[C:2]2=[O:1])[CH2:26][NH:25][CH2:24]1

Participants

5

Reactant 3

HCID 313Hydrochloric AcidHCID 312751,4-DioxaneHCID 67051729HCID 67051729, compound

Product 1

HCID 67051639HCID 67051639, compoundYield 61%

Reagents, catalysts & solvents 1

HCID 887MethanolSolvent

Procedure

A solution of 1,1-dimethylethyl 3-[3,6-dioxo-1,4-bis(phenylmethyl)piperazin-2-yl]-3-hydroxyazetidine-1-carboxylate (1.04 g, 2.2 mmol) in methanol (10 mL) was treated with hydrogen chloride in dioxane (4 N, 5.5 mL, 22 mmol) at 60° C. for 25 min. After cooling to room temperature the solution was concentrated. Ethyl acetate and 2 N hydrochloric acid were added to the residue and the phases were separated. The organic phase was discarded. The aqueous phase was basified with 5 M sodium hydroxide and the resulting solution was extracted 4 times with ethyl acetate. The combined organic extracts were dried over magnesium sulfate, filtered, and concentrated. The residue was purified by column chromatography (85% dichloromethane:14% methanol:1% aqueous ammonium hydroxide) to provide 3-(3-hydroxyazetidin-3-yl)-1,4-bis(phenylmethyl)piperazine-2,5-dione as a colorless film (493 mg, 1.35 mmol, 61% yield). 1H NMR (400 MHz, CDCl3): 7.39-7.28 (m, 6H), 7.25-7.20 (m, 4H), 5.39 (d, 1H), 4.80 (d, 1H), 4.44 (d, 1H), 4.36 (d, 1H), 4.26 (d, 1H), 4.11 (s, 1H), 3.97 (d, 1H), 3.83 (d, 1H), 3.71 (d, 1H), 3.27 (m, 2H); MS (EI) for C21H23N3O3: 366 (MH+).

Workup

  1. concentrationwas concentrated
  2. additionEthyl acetate and 2 N hydrochloric acid were added to the residue
  3. customthe phases were separated
  4. extractionthe resulting solution was extracted 4 times with ethyl acetate
  5. dry with materialThe combined organic extracts were dried over magnesium sulfate
  6. filtrationfiltered
  7. concentrationconcentrated
  8. customThe residue was purified by column chromatography (85% dichloromethane:14% methanol:1% aqueous ammonium hydroxide)

Sources & evidence

ORD record
ord-6a92c24b7dae4ef5b8cf772592f61d87
Source dataset
uspto-grants-2011_08
Patent number
US07999006B2

Reaction notes

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