Sodium Bicarbonate → 143943-72-0

HRID 1728364Notes

Reaction equation

HRID 1728364 reaction equation
[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.N1(OC(N(C)C)=[N+](C)C)C2C=CC=CC=2N=N1.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

Participants

8

Reactant 4

HCID 516892Sodium BicarbonateHCID 2733084Methanaminium, N-((1H-benzotriazol-1-yloxy)(dimethylamino)methylene)-N-methyl-, hexafluorophosphate(1-) (1:1)HCID 14666744HCID 14666744, compoundHCID 22309122(S)-3-Hydroxypyrrolidine hydrochloride

Product 1

HCID 14770131143943-72-0Yield 88.1%

Reagents, catalysts & solvents 3

HCID 962WaterSolventHCID 6228DimethylformamideSolventHCID 79724-MethylmorpholineSolvent

Procedure

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° .

Workup

  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)

Sources & evidence

ORD record
ord-3f6eee209aa2469aa9f87c220ef82d06
Source dataset
uspto-grants-1994_07
Patent number
US05326769

Reaction notes

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