Sodium Hydroxide → Asenapine

HRID 253745ノート

反応式

HRID 253745 の反応式
[Cl-].[Al+3].[Cl-].[Cl-].[H-].[Al+3].[Li+].[H-].[H-].[H-].[Cl:11][C:12]1[CH:31]=[CH:30][C:15]2[O:16][C:17]3[CH:29]=[CH:28][CH:27]=[CH:26][C:18]=3[C@H:19]3[CH2:23][N:22]([CH3:24])[C:21](=O)[C@@H:20]3[C:14]=2[CH:13]=1.[OH-].[Na+]>O1CCCC1.O.C1(C)C=CC=CC=1>[Cl:11][C:12]1[CH:31]=[CH:30][C:15]2[O:16][C:17]3[CH:29]=[CH:28][CH:27]=[CH:26][C:18]=3[C@H:19]3[CH2:23][N:22]([CH3:24])[CH2:21][C@@H:20]3[C:14]=2[CH:13]=1

参加物

8

反応物 4

HCID 14798Sodium HydroxideHCID 6451240Aluminum(III) ChlorideHCID 21226445Aluminium lithium hydrideHCID 54753299Trans-(+-)-11-chloro-2,3,3a,12b-tetrahydro-2-methyl-1h-dibenz[2,3:6,7]oxepino[4,5-c]pyrrol-1-one

生成物 1

HCID 163091Asenapine収率 99%

試薬・触媒・溶媒 3

HCID 962Water溶媒HCID 1140Toluene溶媒HCID 8028Tetrahydrofuran溶媒4 回

反応条件

温度
0 °C

実験手順

Aluminum chloride (6.9 kg) is added in portions to tetrahydrofuran (100 L) at 0° C. Stirring is continued and a 10% solution of lithium aluminum hydride in tetrahydrofuran (35.0 L) is added keeping the temperature below 10° C. The mixture is cooled to 0° C. and stirred for 15 minutes. A solution of trans-11-chloro-2,3,3a,12b-tetrahydro-2-methyl-1H-dibenz[2,3:6,7]oxepino[4,5-c]pyrrol-1-one (IV) (10.0 kg) in tetrahydrofuran (100 L) is added to the mixture while keeping the temperature below 15° C. Tetrahydrofuran (5 L) is added, stirring is continued for 1 hour at 10° C., and 0.6 N sodium hydroxide solution (100 L) is added keeping the temperature below 10° C. Stirring is continued for 15 minutes at 20° C. and toluene (150 L) and of water (100 L) are added. Stirring is continued for 15 minutes at 20° C. and the salt layer is separated. The salt layer is extracted with toluene (2×50 L). The combined filtrates are separated and the aqueous layer is extracted with of toluene (50 L). The combined organic layers are evaporated in vacuum at 70° C. to give trans-5-chloro-2,3,3a,12b-tetrahydro-2-methyl-1H-dibenz[2,3:6,7]oxepino[4,5-c]pyrrole (A) (9.4 kg, 99%); 1H-NMR (400.13 MHz in CDCl3 relative to TMS) δ 2.54 (s, 3H), 3.15 (m, 2H), 3.25 and 3.61 (2×M, 4H), 7.01-7.36 (m, 7H).

後処理

  1. customthe temperature below 10° C
  2. stirringstirred for 15 minutes
  3. customthe temperature below 15° C
  4. stirringstirring
  5. customthe temperature below 10° C
  6. stirringStirring
  7. waitis continued for 15 minutes at 20° C.
  8. stirringStirring
  9. waitis continued for 15 minutes at 20° C.
  10. customthe salt layer is separated
  11. extractionThe salt layer is extracted with toluene (2×50 L)
  12. customThe combined filtrates are separated
  13. extractionthe aqueous layer is extracted with of toluene (50 L)
  14. customThe combined organic layers are evaporated in vacuum at 70° C.

出典と根拠

ORDレコード
ord-3cdc1d10c3d04e33b158a2904e5ee3b5
出典データセット
uspto-grants-2011_01
特許番号
US07872147B2

反応ノート

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