Water → tert-butyl 7-bromo-8-carbamoyl-6-chloro-3,4-dihydropyrrolo[1,2-a]pyrazine-2(1H)-carboxylate

HRID 589865

Reaktionsgleichung

Reaktionsgleichung von HRID 589865
[C:1]([C:4]1[CH:5]=[C:6]([Cl:20])[N:7]2[CH2:12][CH2:11][N:10]([C:13]([O:15][C:16]([CH3:19])([CH3:18])[CH3:17])=[O:14])[CH2:9][C:8]=12)(=[O:3])[NH2:2].C(OCC)(=O)C.[Br:27]N1C(=O)CCC1=O.O>ClCCl>[Br:27][C:5]1[C:4]([C:1](=[O:3])[NH2:2])=[C:8]2[CH2:9][N:10]([C:13]([O:15][C:16]([CH3:17])([CH3:19])[CH3:18])=[O:14])[CH2:11][CH2:12][N:7]2[C:6]=1[Cl:20]

Komponenten

6

Edukt 4

HCID 962WaterHCID 8857Ethyl AcetateHCID 67184N-bromobutanimideHCID 66585106tert-butyl 8-carbamoyl-6-chloro-3,4-dihydropyrrolo[1,2-a]pyrazine-2(1H)-carboxylate

Produkt 1

HCID 66585083tert-butyl 7-bromo-8-carbamoyl-6-chloro-3,4-dihydropyrrolo[1,2-a]pyrazine-2(1H)-carboxylateAusbeute 37,6 %

Reagenzien, Katalysatoren, Lösungsmittel 1

HCID 6344DichloromethaneLösungsmittel2×

Reaktionsbedingungen

Temperatur
0 °C

Versuchsvorschrift

To a solution of 10.5 g (35.1 mmol) of tert-butyl 8-carbamoyl-6-chloro-3,4-dihydropyrrolo[1,2-a]pyrazine-2(1H)-carboxylate in 1 l of a mixture of 50% ethyl acetate in dichloromethane precooled to 0° C. is added slowly a solution of 6.90 g (38.6 mmol) of N-bromosuccinimide in 200 ml of dichloromethane. The reaction is stirred for 5 hours at 0° C. and then for 12 hours while allowing the temperature to return to room temperature. 300 ml of water are then added, the organic phase is separated out by settling and the aqueous phase is then washed with twice 200 ml of ethyl acetate. The organic phases are combined and partially concentrated under reduced pressure. The solution is taken up in 60 ml of water and the organic solvents are removed by evaporation under reduced pressure. The insoluble matter suspended in water is isolated by filtration, washed with water and then dried under reduced pressure in the presence of phosphorus pentoxide. The residue obtained is chromatographed on a column of silica gel, eluting with a mixture of 5 to 50% ethyl acetate in dichloromethane, to give 5.0 g of tert-butyl 7-bromo-8-carbamoyl-6-chloro-3,4-dihydropyrrolo[1,2-a]pyrazine-2(1H)-carboxylate in the form of a white solid after triturating in ethyl acetate and drying at 60° C. under reduced pressure.

Aufarbeitung

  1. customprecooled to 0° C.
  2. waitfor 12 hours while allowing
  3. customto return to room temperature
  4. customthe organic phase is separated out
  5. washthe aqueous phase is then washed with twice 200 ml of ethyl acetate
  6. concentrationpartially concentrated under reduced pressure
  7. customthe organic solvents are removed by evaporation under reduced pressure
  8. customis isolated by filtration
  9. washwashed with water
  10. dry with materialdried under reduced pressure in the presence of phosphorus pentoxide
  11. customThe residue obtained
  12. customis chromatographed on a column of silica gel
  13. washeluting with a mixture of 5 to 50% ethyl acetate in dichloromethane

Quellen und Nachweise

ORD-Eintrag
ord-30a8a160e45e4d76897c633d8c8e0148
Quelldatensatz
uspto-grants-2016_01
Patentnummer
US09233965B2

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