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Hydrochloric Acid → Quetiapine

HRID 2246819
ノート
印刷プレビュー

反応式

HRID 2246819 の反応式
Cl[C:2]1[C:8]2[CH:9]=[CH:10][CH:11]=[CH:12][C:7]=2[S:6][C:5]2[CH:13]=[CH:14][CH:15]=[CH:16][C:4]=2[N:3]=1.OCCO[CH:21]([N:23]1[CH2:28][CH2:27][NH:26][CH2:25][CH2:24]1)[CH3:22].[C:29](=[O:32])(O)[O-].[C:33](=O)(O)[OH:34].[Na+].Cl>[Br-].C([N+](CCCC)(CCCC)CCCC)CCC.C1(C)C=CC=CC=1>[OH:34][CH2:33][CH2:29][O:32][CH2:22][CH2:21][N:23]1[CH2:24][CH2:25][N:26]([C:2]2[C:8]3[CH:9]=[CH:10][CH:11]=[CH:12][C:7]=3[S:6][C:5]3[CH:13]=[CH:14][CH:15]=[CH:16][C:4]=3[N:3]=2)[CH2:27][CH2:28]1
参加物実験手順後処理出典と根拠反応ノート

参加物

7

反応物 4

HCID 313Hydrochloric AcidHCID 1058648111-Chlorodibenzo(b,f)(1,4)thiazepineHCID 193588281-(2-Hydroxyethoxy)ethylpiperazineHCID 23696331Sodium bicarbonate carbonate

生成物 1

HCID 5002Quetiapine収率 78.2%

試薬・触媒・溶媒 2

HCID 74236
Tetrabutylammonium Bromide
触媒
HCID 1140Toluene溶媒

実験手順

A 1 liter round bottom flask equipped with stirring rod, thermo pocket, reflux condenser and nitrogen inlet was charged with 10 gm (0.04 moles) of 11-chlorodibenzo[b,f][1,4]-thiazepine (I), 100 cc toluene and the mixture was stirred for 15 min. at room temperature. The resulting solution was combined with 7.7 gm (0.044 mole) of 1-(2-hydroxyethoxy)ethylpiperazine (II), 8.5 gm (0.08 mole) of sodium carbonate carbonate and 7.7 gm (0.24 mole) of tetra butyl ammonium bromide. The reaction mixture was heated at gentle reflux for 22 hrs and a sample of the reaction mixture was analyzed by HPLC. The analysis revealed that less than 2% of the starting material remained. The reaction mixture was cooled to room temperature and combined with 300 cc 1N hydrochloric acid solution to get a pH in between 1 to 2. The layers were separated and the aqueous layer was diluted with 100 cc toluene and pH was adjusted between 8 to 9 by addition of sodium carbonate. The layers (aqueous and nonaqueous reaction solvent toluene) were separated and the aqueous layer was extracted with 100 cc toluene. The organic (toluene) layers were combined and washed with 2×100 cc of water. The reaction solvent (toluene) was distilled-off under vacuum at 70 to 80° C. to afford 12 gm oil. HPLC area %: 98.87

後処理

  1. customA 1 liter round bottom flask equipped
  2. temperaturethermo pocket, reflux condenser and nitrogen inlet
  3. stirringthe mixture was stirred for 15 min. at room temperature
  4. temperatureThe reaction mixture was heated
  5. temperatureat gentle reflux for 22 hrs
  6. customto get a pH in between 1 to 2
  7. customThe layers were separated
  8. additionthe aqueous layer was diluted with 100 cc toluene and pH
  9. additionwas adjusted between 8 to 9 by addition of sodium carbonate
  10. customThe layers (aqueous and nonaqueous reaction solvent toluene) were separated
  11. extractionthe aqueous layer was extracted with 100 cc toluene
  12. washwashed with 2×100 cc of water
  13. customwas distilled-off under vacuum at 70 to 80° C.

出典と根拠

ORDレコード
ord-ad05d79c89684fa19fdf5f4bb5fefdb4
出典データセット
uspto-grants-2010_03
DOI
10.6084/m9.figshare.5104873.v1
特許番号
US07687622B2

反応ノート

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