Pyridine → Topiramate

HRID 273908노트

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HRID 273908 반응식
[CH3:1][C:2]1([CH3:18])[O:10][C@@H:9]2[C@@H:4]([CH2:5][O:6][C@@:7]3([CH2:16][OH:17])[O:13][C:12]([CH3:15])([CH3:14])[O:11][C@H:8]32)[O:3]1.[N:19]1C=CC=CC=1.[S:25](Cl)(Cl)(=[O:27])=[O:26]>C(Cl)Cl>[CH3:1][C:2]1([CH3:18])[O:10][C@@H:9]2[C@@H:4]([CH2:5][O:6][C@@:7]3([CH2:16][O:17][S:25]([NH2:19])(=[O:27])=[O:26])[O:13][C:12]([CH3:14])([CH3:15])[O:11][C@H:8]32)[O:3]1

참가 물질

5

반응물 3

HCID 1049PyridineHCID 24648Sulfuryl chlorideHCID 102443452,3:4,5-Di-o-isopropylidene-beta-D-fructopyranose

생성물 1

HCID 5284627Topiramate수율 244%

시약·촉매·용매 1

HCID 6344Dichloromethane용매3회

실험 절차

Under nitrogen, a solution of the alcohol of Example 1 (15.0 g, 0.0576 mol) and pyridine (15 mL, 0.18 mol) in methylene chloride (60 mL) was cooled to -40° C. in a dry ice/isopropanol bath. With stirring, a solution of sulfuryl chloride (16.0 g, 0.118 mol) in methylene chloride (10 mL) was added gradually (approx. 50 minutes) so that the temperature did not exceed -25° C. The ice bath was removed as soon as the addition was complete and the reaction mixture stirred for an additional 2 h. During this time the light yellow precipitate became a clumpy brown solid. Solvent was removed in vacuo to yield a sticky, brown residue. The residue was dissolved in 100 mL methylene chloride and anhydrous ammonia was bubbled through the mixture overnight at ambient temperature. The dark reaction mixture was concentrated in vacuo to give 47.7 g of the title compound as a black residue. The crude product was found to be 15.10% pure by GLC giving a corrected yield of 36.83 %.

후처리

  1. customdid not exceed -25° C
  2. customThe ice bath was removed as
  3. additionsoon as the addition
  4. stirringthe reaction mixture stirred for an additional 2 h
  5. customSolvent was removed in vacuo
  6. customto yield a sticky, brown residue
  7. customanhydrous ammonia was bubbled through the mixture overnight at ambient temperature
  8. customThe dark reaction mixture
  9. concentrationwas concentrated in vacuo

출처 및 근거

ORD 기록
ord-569c3dcb837f4c9c859d4a8cc35bf0a7
출처 데이터셋
uspto-grants-1995_02
특허 번호
US05387700

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