Toluene → Alprazolam

HRID 425231

反応式

HRID 425231 の反応式
[C:1]([NH:4][NH:5][CH:6]1[CH:12]=[N:11][C:10]([C:13]2[CH:18]=[CH:17][CH:16]=[CH:15][CH:14]=2)=[C:9]2[CH:19]=[C:20]([Cl:23])[CH:21]=[CH:22][C:8]2=[N:7]1)(=O)[CH3:2].C1(C)C=CC=CC=1.C1(C)C=CC(S(O)(=O)=O)=CC=1>O>[CH3:2][C:1]1[N:7]2[C:8]3[CH:22]=[CH:21][C:20]([Cl:23])=[CH:19][C:9]=3[C:10]([C:13]3[CH:18]=[CH:17][CH:16]=[CH:15][CH:14]=3)=[N:11][CH2:12][C:6]2=[N:5][N:4]=1

参加物

5

反応物 3

HCID 1140Toluene2 回HCID 6101p-Toluenesulfonic acidHCID 667050232-(2-Acetyl hydrazino)-7-chloro-5-phenyl-2h-1,4 benzodiazepine

生成物 1

HCID 2118Alprazolam収率 80%

試薬・触媒・溶媒 1

HCID 962Water溶媒

反応条件

温度
92.5 °C

実験手順

2-(2-acetyl hydrazino)-7-chloro-5-phenyl-2H-1,4 benzodiazepine (117.5 g; 0.36 mole) and toluene (11.75 mole.) were added to a RB flask. 0.94 mole of toluene was distilled out at 110-112° C. The reaction mixture was cooled to 90-95° C. and charged with p-toluene sulphonic acid (0.0012 mole). The reaction mixture was then refluxed at 105-110° C. for 10-12 hrs with a Dean-Stark apparatus for water removal. At the end of the reaction (as indicated by TLC), reaction mixture was cooled to 25-30° C. The reaction mass was then further cooled to 10-15° C. and stirred at same temperature for 4-5 hrs. The solids precipitated were filtered and washed with cold toluene to obtain crude 8-chloro-1-methyl-6-phenyl-4H-s-trizolo[4 3-I][1,4] benzodiazepine (alprazolam). The crude alprazolam was purified from isopropanol to obtain 80% yield of pure alprazolam.

後処理

  1. customAt the end of the reaction (as indicated by TLC), reaction mixture
  2. temperaturewas cooled to 25-30° C
  3. temperatureThe reaction mass was then further cooled to 10-15° C.
  4. customThe solids precipitated
  5. filtrationwere filtered
  6. washwashed with cold toluene
  7. customto obtain crude 8-chloro-1-methyl-6-phenyl-4H-s-trizolo[4 3-I][1,4] benzodiazepine (alprazolam)
  8. customThe crude alprazolam was purified from isopropanol

出典と根拠

ORDレコード
ord-1bf2ef2791c64e8ea6cda7ee1670141f
出典データセット
uspto-grants-2012_01
特許番号
US08106189B2

関連ノート

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