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

HRID 576725노트

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HRID 576725 반응식
[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]

참가 물질

6

반응물 4

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

생성물 1

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

시약·촉매·용매 1

HCID 6422Trifluoroacetic acid용매

실험 절차

(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).

후처리

  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)

출처 및 근거

ORD 기록
ord-8981c7acbe9146aba529c96dc304a23d
출처 데이터셋
uspto-grants-2015_05
특허 번호
US09040534B2

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