Toluene → Irbesartan

HRID 1715733

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HRID 1715733 반응식
Br[CH2:2][C:3]1[CH:8]=[CH:7][C:6]([C:9]2[CH:14]=[CH:13][CH:12]=[CH:11][C:10]=2[C:15]2[N:19](C(C3C=CC=CC=3)(C3C=CC=CC=3)C3C=CC=CC=3)[N:18]=[N:17][N:16]=2)=[CH:5][CH:4]=1.C1(C)C=CC=CC=1.[OH-].[K+].Cl.[CH2:49]([C:53]1[NH:57][C:56](=[O:58])[C:55]2([CH2:62][CH2:61][CH2:60][CH2:59]2)[N:54]=1)[CH2:50][CH2:51][CH3:52]>[N+](CCCC)(CCCC)(CCCC)CCCC.[O-]S(O)(=O)=O.O>[CH3:52][CH2:51][CH2:50][CH2:49][C:53]1[N:57]([CH2:2][C:3]2[CH:4]=[CH:5][C:6]([C:9]3[CH:14]=[CH:13][CH:12]=[CH:11][C:10]=3[C:15]3[N:16]=[N:17][NH:18][N:19]=3)=[CH:7][CH:8]=2)[C:56](=[O:58])[C:55]2([CH2:62][CH2:61][CH2:60][CH2:59]2)[N:54]=1

참가 물질

7

반응물 4

HCID 1140TolueneHCID 14797Potassium 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

생성물 1

HCID 3749Irbesartan수율 84%

시약·촉매·용매 2

HCID 94433Tetrabutylammonium hydrogen sulfate촉매HCID 962Water용매

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온도
90 °C

실험 절차

5-(4′-bromomethyl-biphenyl-2-yl)-1-trityl-1H-tetrazole (24.6 g) was charged to toluene (240 ml). To this, a solution of KOH (10.4 g), 2n-butyl-1,3-diazaspiro (4,4) non-1-en-4 one HCl (12.0 g) and Bu4NHSO4 (1.8 g) in water (40 ml) was added. The two-phase mixture was then heated to 90° C. for 90 minutes under vigorous stirring. The reaction mixture was cooled to room temperature. The toluene layer was separated and the aqueous phase was extracted with toluene (50 ml). The combined organic layer was evaporated. The residue was dissolved in acetone (100 ml) and 3N HCl (52 ml) and stirred at room temperature (TLC monitoring). A solution of KOH (14.6 g) in water (100 ml) was slowly added and acetone was evaporated under reduced pressure. The precipitated trityl alcohol was filtered and washed with water (2×50 ml). The filtrate was washed with toluene and slowly acidified to pH 4.0 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 (2×25 ml) and dried under reduced pressure at 50-60° C. to yield irbesartan free base (84%).

후처리

  1. temperatureThe reaction mixture was cooled to room temperature
  2. customThe toluene layer was separated
  3. extractionthe aqueous phase was extracted with toluene (50 ml)
  4. customThe combined organic layer was evaporated
  5. dissolutionThe residue was dissolved in acetone (100 ml)
  6. additionA solution of KOH (14.6 g) in water (100 ml) was slowly added
  7. customacetone was evaporated under reduced pressure
  8. filtrationThe precipitated trityl alcohol was filtered
  9. washwashed with water (2×50 ml)
  10. washThe filtrate was washed with toluene
  11. temperatureThe suspension was cooled to 0-4° C.
  12. stirringstirred for an additional 30 minutes
  13. filtrationfiltered
  14. washThe cake was washed with cold isopropanol (2×25 ml)
  15. customdried under reduced pressure at 50-60° C.

출처 및 근거

ORD 기록
ord-d927150c0f89466487c75930c35a7c6b
출처 데이터셋
uspto-grants-2010_09
특허 번호
US07799928B2

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