Hydrochloric Acid → Tert-butyl 4-oxo-octahydropiperazino[2,1-c]morpholine-8-carboxylate

HRID 2063311Notizen

Reaktionsgleichung

Reaktionsgleichung von HRID 2063311
[OH:1][CH2:2][CH:3]1[NH:8][CH2:7][CH2:6][N:5]([C:9]([O:11][C:12]([CH3:15])([CH3:14])[CH3:13])=[O:10])[CH2:4]1.C(N(CC)CC)C.Cl[CH2:24][C:25](Cl)=[O:26].OS([O-])(=O)=O.[K+].[H-].[Na+].Cl.[OH-].[Na+]>C(Cl)Cl.CN(C=O)C.C(OCC)(=O)C>[O:26]=[C:25]1[CH2:24][O:1][CH2:2][CH:3]2[CH2:4][N:5]([C:9]([O:11][C:12]([CH3:15])([CH3:14])[CH3:13])=[O:10])[CH2:6][CH2:7][N:8]12

Komponenten

11

Edukt 7

HCID 313Hydrochloric AcidHCID 6577Chloroacetyl chlorideHCID 8471TriethylamineHCID 14798Sodium HydroxideHCID 24758Sodium hydrideHCID 516920Potassium bisulfateHCID 223865084-N-Boc-2-hydroxymethylpiperazine

Produkt 1

HCID 16123288Tert-butyl 4-oxo-octahydropiperazino[2,1-c]morpholine-8-carboxylateAusbeute 21 %

Reagenzien, Katalysatoren, Lösungsmittel 3

HCID 6228DimethylformamideLösungsmittelHCID 6344DichloromethaneLösungsmittel2×HCID 8857Ethyl AcetateLösungsmittel

Reaktionsbedingungen

Temperatur
0 °C

Versuchsvorschrift

To a solution of tert-butyl 3-(hydroxymethyl)piperazine-1-carboxylate (360 mg, 1.7 mmol) in methylene chloride (10 mL) was added triethylamine (505 mg, 5.0 mmol) at 0° C. Chloroacetyl chloride (282 mg, 2.5 mmol) was dissolved in methylene chloride (5 mL) and the solution was added to the former solution drop by drop at 0° C. The reaction mixture was stirred at 0° C. for 1 h and then at RT for 3 h. An aqueous solution of KHSO4 (1M, 5 mL) was added and then the organic phase was separated by means of a phase separator column. The solvent was removed by evaporation and the amide intermediate, which was purified by silica gel chromatography, was dissolved in DMF (2 mL). While cooling and under nitrogen the solution was added drop wise to a suspension of NaH (60 mg, 2.5 mmol) in DMF. The mixture was stirred at RT for 48 h, then diluted with ethyl acetate and then pored over aqueous HCl (0.5 M). The pH was adjusted to 12 with NaOH and then the organic phase was separated. The solvent was removed by evaporation and the product was purified by silica gel chromatography. There was obtained 90 mg (21%) of tert-butyl 4-oxohexahydropyrazino[2,1-c][1,4]oxazine-8(1H)-carboxylate. 1H NMR (500 MHz, CDCl3): 1.4 (s, 9H), 2.5-2.7 (m, 2H), 2.8 (m, 1H), 3.4-3.5 (m, 2H), 3.9-4.2 (m, 5H), 4.5 (d, 1H); LCMS: m/z 257 (M+1)+.

Aufarbeitung

  1. additionthe solution was added to the former solution drop by drop at 0° C
  2. waitat RT for 3 h
  3. customthe organic phase was separated by means of a phase separator column
  4. customThe solvent was removed by evaporation
  5. customthe amide intermediate, which was purified by silica gel chromatography
  6. dissolutionwas dissolved in DMF (2 mL)
  7. temperatureWhile cooling and under nitrogen the solution
  8. additionwas added drop
  9. stirringThe mixture was stirred at RT for 48 h
  10. customthe organic phase was separated
  11. customThe solvent was removed by evaporation
  12. customthe product was purified by silica gel chromatography

Quellen und Nachweise

ORD-Eintrag
ord-4be2187cd92c4363befbc41d01080f0d
Quelldatensatz
uspto-grants-2012_10
Patentnummer
US08288370B2

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