Sodium Bicarbonate → Ro-41-3290

HRID 1198770ノート

反応式

HRID 1198770 の反応式
[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

参加物

8

反応物 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

生成物 1

HCID 14770131Ro-41-3290収率 88.1%

試薬・触媒・溶媒 3

HCID 962Water溶媒HCID 6228Dimethylformamide溶媒HCID 79724-Methylmorpholine溶媒

実験手順

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°.

後処理

  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)

出典と根拠

ORDレコード
ord-9e6fbc24c17241d49ab8189b5d295b7f
出典データセット
uspto-grants-1994_01
特許番号
US05281711

反応ノート

読み込み中…