Sodium Bicarbonate → Ro-41-3290

HRID 1198770Notizen

Reaktionsgleichung

Reaktionsgleichung von HRID 1198770
[Cl:1][C:2]1[CH:3]=[CH:4][C:5]2[CH2:14][CH2:13][N:12]3[C:7](=[C:8]([C:22](O)=[O:23])[CH:9]=[C:10]([C:16]4[CH:21]=[CH:20][CH:19]=[CH:18][CH:17]=4)[C:11]3=[O:15])[C:6]=2[CH:25]=1.Cl.[OH:27][C@H:28]1[CH2:32][CH2:31][NH:30][CH2:29]1.F[P-](F)(F)(F)(F)F.C[N+](C)=C(N(C)C)O.C(=O)([O-])O.[Na+]>CN(C)C=O.CN1CCOCC1.O>[Cl:1][C:2]1[CH:3]=[CH:4][C:5]2[CH2:14][CH2:13][N:12]3[C:7](=[C:8]([C:22]([N:30]4[CH2:31][CH2:32][C@H:28]([OH:27])[CH2:29]4)=[O:23])[CH:9]=[C:10]([C:16]4[CH:17]=[CH:18][CH:19]=[CH:20][CH:21]=4)[C:11]3=[O:15])[C:6]=2[CH:25]=1

Komponenten

8

Edukt 4

HCID 516892Sodium BicarbonateHCID 1466674410-Chloro-4-oxo-3-phenyl-6,7-dihydro-4H-pyrido[2,1-A]isoquinoline-1-carboxylic acidHCID 21864398Tetramethyluronium hexafluorophosphateHCID 22309122(S)-3-Hydroxypyrrolidine hydrochloride

Produkt 1

HCID 14770131Ro-41-3290Ausbeute 88,1 %

Reagenzien, Katalysatoren, Lösungsmittel 3

HCID 962WaterLösungsmittelHCID 6228DimethylformamideLösungsmittelHCID 79724-MethylmorpholineLösungsmittel

Versuchsvorschrift

70.36 g of 10-chloro-6,7-dihydro-4-oxo-3-phenyl-4H-benzo[a]quinolizine-1-carboxylic acid are dissolved in 1600 ml of N,N-dimethylformamide under argon, whereupon 45 ml of 4-methylmorpholine, 27.2 g of (S)-3-hydroxypyrrolidine hydrochloride and 83.4 g of O-benzotriazol-1-yl-,N,N,N',N'-tetramethyluronium hexafluorophosphate are added in succession. The mixture is stirred at room temperature for about 18 hours and the yellow solution obtained is poured into 6000 ml of water and treated slowly with 2500 ml of saturated sodium hydrogen carbonate solution. The product obtained is filtered under suction and washed with 1000 ml of water. After drying in a vacuum at 70° there are obtained 83.3 g of crude product. By repeated recrystallization from a 120-fold amount of isopropanol and chromatography of the combined mother liquours on 1000 g of silica gel with methylene chloride/diethyl ether (9:1) and subsequently with methylene chloride/acetone (9:1), there are obtained 74.2 g (88%) of (S)-1-[ (10-chloro-6,7-dihydro-4-oxo-3-phenyl-4H-benzo[a]quinolizin-1-yl)carbonyl]-3-hydroxypyrrolidine with a m.p. of 257°-259°.

Aufarbeitung

  1. additionare added in succession
  2. customthe yellow solution obtained
  3. customThe product obtained
  4. filtrationis filtered under suction
  5. washwashed with 1000 ml of water
  6. customAfter drying in a vacuum at 70°
  7. customthere are obtained 83.3 g of crude product
  8. customrecrystallization from a 120-fold amount of isopropanol and chromatography of the combined mother liquours on 1000 g of silica gel with methylene chloride/diethyl ether (9:1)

Quellen und Nachweise

ORD-Eintrag
ord-9e6fbc24c17241d49ab8189b5d295b7f
Quelldatensatz
uspto-grants-1994_01
Patentnummer
US05281711

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