Potassium Hydroxide → Irbesartan

HRID 1715731

反応式

HRID 1715731 の反応式
[OH-].[Na+].Br[CH2:4][C:5]1[CH:10]=[CH:9][C:8]([C:11]2[CH:16]=[CH:15][CH:14]=[CH:13][C:12]=2[C:17]2[N:21](C(C3C=CC=CC=3)(C3C=CC=CC=3)C3C=CC=CC=3)[N:20]=[N:19][N:18]=2)=[CH:7][CH:6]=1.Cl.[CH2:42]([C:46]1[NH:50][C:49](=[O:51])[C:48]2([CH2:55][CH2:54][CH2:53][CH2:52]2)[N:47]=1)[CH2:43][CH2:44][CH3:45].[OH-].[K+]>O.[Br-].C([N+](CCCC)(CCCC)CCCC)CCC.C1(C)C=CC=CC=1>[CH3:45][CH2:44][CH2:43][CH2:42][C:46]1[N:50]([CH2:4][C:5]2[CH:6]=[CH:7][C:8]([C:11]3[CH:16]=[CH:15][CH:14]=[CH:13][C:12]=3[C:17]3[N:18]=[N:19][NH:20][N:21]=3)=[CH:9][CH:10]=2)[C:49](=[O:51])[C:48]2([CH2:55][CH2:54][CH2:53][CH2:52]2)[N:47]=1

参加物

8

反応物 4

HCID 14797Potassium HydroxideHCID 14798Sodium HydroxideHCID 100534615-(4'-(Bromomethyl)(1,1'-biphenyl)-2-yl)-1-trityl-1H-tetraazoleHCID 101769952-Butyl-1,3-diazaspiro(4.4)non-1-en-4-one hydrochloride

生成物 1

HCID 3749Irbesartan収率 92%

試薬・触媒・溶媒 3

HCID 74236Tetrabutylammonium Bromide触媒HCID 962Water溶媒2 回HCID 1140Toluene溶媒

反応条件

温度
85 °C

実験手順

16.4 g of sodium hydroxide dissolved in 240 ml of purified water was added to the mixture of 5-(4′-bromomethyl-biphenyl-2-yl)-1-trityl-1H-tetrazole (59.5 g) and 2n-butyl-1,3-diazaspiro (4,4) non-1-en-4-one HCl (25 g) and tetra butyl ammonium bromide (2.15 g) in toluene (250 ml). The mixture was heated to about 85° C. for about 2 hours. After reaction completion, the reaction mass was cooled to about 25° C. and the toluene layer separated. The aqueous phase was extracted with toluene (105 ml). The combined organic layer was evaporated. The residue was dissolved in acetone (208 ml) and 3N HCl was added (600 ml). The contents were stirred at room temperature until reaction completion (as monitored by TLC). After reaction completion, a solution of KOH (30.4 g) in water (208 ml) was slowly added and acetone was evaporated under reduced pressure. The precipitated trityl alcohol was filtered and washed with water (2×105 ml). The filtrate was washed with toluene and slowly acidified to pH 4 with 3 N HCl. The suspension was cooled to 0-4° C., stirred for an additional 30 minutes and filtered. The cake was washed with cold isopropanol (2×50 ml) and dried under reduced pressure at 50-60° C. to yield irbesartan free base (92.0%).

後処理

  1. customAfter reaction completion
  2. temperaturethe reaction mass was cooled to about 25° C.
  3. customthe toluene layer separated
  4. extractionThe aqueous phase was extracted with toluene (105 ml)
  5. customThe combined organic layer was evaporated
  6. dissolutionThe residue was dissolved in acetone (208 ml)
  7. addition3N HCl was added (600 ml)
  8. customAfter reaction completion
  9. customacetone was evaporated under reduced pressure
  10. filtrationThe precipitated trityl alcohol was filtered
  11. washwashed with water (2×105 ml)
  12. washThe filtrate was washed with toluene
  13. temperatureThe suspension was cooled to 0-4° C.
  14. stirringstirred for an additional 30 minutes
  15. filtrationfiltered
  16. washThe cake was washed with cold isopropanol (2×50 ml)
  17. customdried under reduced pressure at 50-60° C.

出典と根拠

ORDレコード
ord-1c7ab24aee014bf79d437d20d7be988e
出典データセット
uspto-grants-2010_09
特許番号
US07799928B2

関連ノート

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