4-(4-Fluorobenzoyl)piperidine → 8-[4-(4-Fluoro-Benzoyl)-Piperidin-1-Ylmethyl]-1,3,7,8-Tetrahydro-6,9-Dioxa-1,3-Diaza-Cyclopenta[a]Naphthalen-2-One

HRID 982679노트

반응식

HRID 982679 반응식
CC1C=CC(S(O[CH2:12][C@@H:13]2[O:26][C:17]3[C:18]4[NH:22][C:21](=[O:23])[NH:20][C:19]=4[CH:24]=[CH:25][C:16]=3[O:15][CH2:14]2)(=O)=O)=CC=1.[F:27][C:28]1[CH:41]=[CH:40][C:31]([C:32]([CH:34]2[CH2:39][CH2:38][NH:37][CH2:36][CH2:35]2)=[O:33])=[CH:30][CH:29]=1>CS(C)=O.C(OCC)(=O)C>[F:27][C:28]1[CH:29]=[CH:30][C:31]([C:32]([CH:34]2[CH2:39][CH2:38][N:37]([CH2:12][CH:13]3[O:26][C:17]4[C:16](=[CH:25][CH:24]=[C:19]5[NH:20][C:21](=[O:23])[NH:22][C:18]5=4)[O:15][CH2:14]3)[CH2:36][CH2:35]2)=[O:33])=[CH:40][CH:41]=1

참가 물질

5

반응물 2

HCID 27244404-(4-Fluorobenzoyl)piperidineHCID 11428826(8R)-1,3,7,8-tetrahydro-8-[[[(4-methylphenyl)sulfonyl]oxy]methyl]-2H-[1,4]dioxino[2,3-e]benzimidazol-2-one

생성물 1

HCID 102730298-[4-(4-Fluoro-Benzoyl)-Piperidin-1-Ylmethyl]-1,3,7,8-Tetrahydro-6,9-Dioxa-1,3-Diaza-Cyclopenta[a]Naphthalen-2-One

시약·촉매·용매 2

HCID 679Dimethyl Sulfoxide용매HCID 8857Ethyl Acetate용매

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온도
90 °C

실험 절차

A mixture of 0.60 g (1.6 mmole) of (8R)-1,3,7,8-tetrahydro-8-[[[(4 methylphenyl)sulfonyl]oxy]methyl]-2H-[1,4]dioxino[2,3-e]benzimidazol-2-one and 1.7 g (8.0 mmole) of 4-(4-fluorobenzoyl)piperidine in 30 mL of DMSO was heated at in 90° C. under nitrogen for 5 hours. The reaction was allowed to come to room temperature, diluted to 500 mL with ethyl acetate, washed with 500 mL portions of saturated aqueous sodium bicarbonate and water, dried over sodium sulfate, filtered and evaporated in vacuum. The residue was column chromatographed on silica gel with 2% methanol in chloroform as eluant and the product fractions evaporated to give the free base as a colorless oil. This was recrystallized from ethanol with the addition of 4 N isopropanolic HCl to give 0.13 g of the (S)-enantiomer of the title compound. A second recrystallization from ethanol gave 0.095 g of the product as a white solid hydrochloride, hydrate, m.p. 250-256° C. (d).

후처리

  1. customto come to room temperature
  2. washwashed with 500 mL portions of saturated aqueous sodium bicarbonate and water
  3. dry with materialdried over sodium sulfate
  4. filtrationfiltered
  5. customevaporated in vacuum
  6. customchromatographed on silica gel with 2% methanol in chloroform as eluant
  7. customthe product fractions evaporated

출처 및 근거

ORD 기록
ord-e071e2f576b847cebe66fd780629f2e1
출처 데이터셋
uspto-grants-2005_03
특허 번호
US06861434B2

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