Triethylamine → (8aR)-2-[1-(diphenylmethyl)azetidin-3-yl]hexahydropyrrolo[1,2-a]pyrazin-6(2H)-one

HRID 2063302Notizen

Reaktionsgleichung

Reaktionsgleichung von HRID 2063302
[CH2:1]1[NH:6][CH2:5][CH2:4][N:3]2[C:7](=[O:10])[CH2:8][CH2:9][C@H:2]12.CS(O[CH:16]1[CH2:19][N:18]([CH:20]([C:27]2[CH:32]=[CH:31][CH:30]=[CH:29][CH:28]=2)[C:21]2[CH:26]=[CH:25][CH:24]=[CH:23][CH:22]=2)[CH2:17]1)(=O)=O.C(N(CC)CC)C>C(#N)C>[C:21]1([CH:20]([C:27]2[CH:32]=[CH:31][CH:30]=[CH:29][CH:28]=2)[N:18]2[CH2:19][CH:16]([N:6]3[CH2:5][CH2:4][N:3]4[C:7](=[O:10])[CH2:8][CH2:9][C@@H:2]4[CH2:1]3)[CH2:17]2)[CH:22]=[CH:23][CH:24]=[CH:25][CH:26]=1

Komponenten

5

Edukt 3

HCID 8471TriethylamineHCID 27587161-(Diphenylmethyl)azetidin-3-yl methanesulfonateHCID 11378540(R)-Hexahydropyrrolo[1,2-a]pyrazin-6(2H)-one

Produkt 1

HCID 16124368(8aR)-2-[1-(diphenylmethyl)azetidin-3-yl]hexahydropyrrolo[1,2-a]pyrazin-6(2H)-oneAusbeute 54 %

Reagenzien, Katalysatoren, Lösungsmittel 1

HCID 6342AcetonitrileLösungsmittel

Reaktionsbedingungen

Temperatur
150 °C

Versuchsvorschrift

(8aR)-Hexahydropyrrolo[1,2-a]pyrazin-6(2H)-one (see WO 03/066635; 0.17 g, 1.2 mmol), 1-(diphenylmethyl)azetidin-3-yl methanesulfonate (see J. Org. Chem.; 56; 1991; 6729; 0.40 g, 1.3 mmol) and triethylamine (0.20 mL, 1.4 mmol) were dissolved in acetonitrile. The mixture was heated for 15 min at 150° C. using microwave single node heating and then the solvent was removed by evaporation. The residue was partitioned between ethyl acetate and aqueous NaHCO3 and the aqueous phase extracted further with ethyl acetate. The organic phase was dried and then the solvent was removed by evaporation. The product was purified by chromatography on silica gel (methanol-methylene chloride 5:95). There was obtained 0.23 g (54%) of (8aR)-2-[1-(diphenylmethyl)azetidin-3-yl]hexahydropyrrolo[1,2-a]pyrazin-6(2H)-one as a pale yellow oil. 1H NMR (500 MHz, CDCl3): 1.5-1.6 (m, 2H), 1.7-1.8 (m, 1H), 2.1-2.2 (m, 1H), 2.3-2.4 (m, 2H), 2.6-2.7 (d, 1H), 2.8 (m, 1H), 2.8-2.9 (m, 3H), 3.0 (qn, 1H), 3.4 (t, 2H), 3.6 (m, 1H), 4.0 (d, 1H), 4.4 (s, 1H), 7.2 (m, 2H), 7.2-7.3 (m, 4H), 7.4 (m, 4H); LCMS: m/z 362 (M+1)+.

Aufarbeitung

  1. temperatureheating
  2. customthe solvent was removed by evaporation
  3. customThe residue was partitioned between ethyl acetate and aqueous NaHCO3
  4. extractionthe aqueous phase extracted further with ethyl acetate
  5. customThe organic phase was dried
  6. customthe solvent was removed by evaporation
  7. customThe product was purified by chromatography on silica gel (methanol-methylene chloride 5:95)

Quellen und Nachweise

ORD-Eintrag
ord-de48cb60ff3843128b899c36de320bd6
Quelldatensatz
uspto-grants-2012_10
Patentnummer
US08288370B2

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