Water → tert-butyl (2S)-2-methyl-5-oxopiperazine-1-carboxylate

HRID 576725Notes

Reaction equation

HRID 576725 reaction equation
[C:1]([O:5][C:6](=[O:16])[NH:7][C@@H:8]([CH3:15])[CH2:9][NH:10][C:11](=[O:14])[CH2:12]Cl)([CH3:4])([CH3:3])[CH3:2].C(=O)([O-])[O-].[K+].[K+].CC(OC(OC(OC(C)(C)C)=O)=O)(C)C.O>FC(F)(F)C(O)=O>[CH3:15][C@H:8]1[CH2:9][NH:10][C:11](=[O:14])[CH2:12][N:7]1[C:6]([O:5][C:1]([CH3:4])([CH3:3])[CH3:2])=[O:16]

Participants

6

Reactant 4

HCID 962WaterHCID 11430Potassium CarbonateHCID 90495Di-tert-butyl dicarbonateHCID 131732867(S)-tert-butyl (1-(2-chloroacetamido)propan-2-yl)carbamate

Product 1

HCID 90402439tert-butyl (2S)-2-methyl-5-oxopiperazine-1-carboxylateYield 78%

Reagents, catalysts & solvents 1

HCID 6422Trifluoroacetic acidSolvent

Procedure

(S)-tert-butyl(1-(2-chloroacetamido)propan-2-yl)carbamate (7.5 g, 29.9 mmol) was dissolved in trifluoroacetic acid (30 mL) and stirred for 10 minutes. The reaction mixture was concentrated, dissolved in THF (321 mL) and potassium carbonate (20.7 g, 149.5 mmol) was added and the reaction mixture was refluxed for 12 hours. To the reaction mixture was added (Boc)2O (7.7 mL, 35.9 mmol) and the reaction mixture was refluxed for an additional 5 hours. The reaction mixture was cooled to rt and water was added. The reaction mixture was extracted with EtOAc. The organic layers were combined, dried with Na2SO4, filtered, concentrated and purified by flash column chromatography (0-100% EtOAc in hexanes) to provide the desired compound (5 g, 78%). 1H NMR (600 MHz, DMSO) δ 8.00 (s, 1H), 4.17 (s, 1H) 3.94 (d, J=17.8 Hz, 1H), 3.58 (d, J=17.9 Hz, 1H), 3.43-3.34 (m, 1H), 3.98 (ddd, J=12.7, 4.9, 2.5 Hz, 1H), 1.43-1.38 (s, 9H), 1.10 (d, J=6.7 Hz, 3H).

Workup

  1. concentrationThe reaction mixture was concentrated
  2. dissolutiondissolved in THF (321 mL)
  3. temperaturethe reaction mixture was refluxed for 12 hours
  4. temperaturethe reaction mixture was refluxed for an additional 5 hours
  5. extractionThe reaction mixture was extracted with EtOAc
  6. dry with materialdried with Na2SO4
  7. filtrationfiltered
  8. concentrationconcentrated
  9. custompurified by flash column chromatography (0-100% EtOAc in hexanes)

Sources & evidence

ORD record
ord-8981c7acbe9146aba529c96dc304a23d
Source dataset
uspto-grants-2015_05
Patent number
US09040534B2

Reaction notes

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