Chlorotrimethylsilane → 2-((1-(4-Methoxy-2,6-dimethylphenylsulfonyl)piperidin-2-yl)methoxy)-1-(4-(1-methyl-piperidin-4-yl)piperazin-1-yl)ethanone dihydrochloride

HRID 2090806

反応式

HRID 2090806 の反応式
COC1C=C(C)C(S(N2CCCCC2COCC(O)=O)(=O)=O)=C(C)C=1.CN1CCC(N2CCNCC2)CC1.C(=O)([O-])O.[Na+].[CH3:44][O:45][C:46]1[CH:51]=[C:50]([CH3:52])[C:49]([S:53]([N:56]2[CH2:61][CH2:60][CH2:59][CH2:58][CH:57]2[CH2:62][O:63][CH2:64][C:65]([N:67]2[CH2:72][CH2:71][N:70]([CH:73]3[CH2:78][CH2:77][N:76]([CH3:79])[CH2:75][CH2:74]3)[CH2:69][CH2:68]2)=[O:66])(=[O:55])=[O:54])=[C:48]([CH3:80])[CH:47]=1.[Cl:81][Si](C)(C)C>ClCCl.C(C(C)=O)C.C(O)C.CC(C)=O.C(OCC)C>[ClH:81].[ClH:81].[CH3:44][O:45][C:46]1[CH:51]=[C:50]([CH3:52])[C:49]([S:53]([N:56]2[CH2:61][CH2:60][CH2:59][CH2:58][CH:57]2[CH2:62][O:63][CH2:64][C:65]([N:67]2[CH2:72][CH2:71][N:70]([CH:73]3[CH2:78][CH2:77][N:76]([CH3:79])[CH2:75][CH2:74]3)[CH2:69][CH2:68]2)=[O:66])(=[O:55])=[O:54])=[C:48]([CH3:80])[CH:47]=1

参加物

10

反応物 5

HCID 6397ChlorotrimethylsilaneHCID 516892Sodium BicarbonateHCID 5663241-(1-Methyl-4-piperidinyl)piperazineHCID 249455742-[1-(4-Methoxy-2,6-dimethyl-phenylsulfonyl)-piperidin-2-ylmethoxy]-1-[4-(1-methyl-piperidin-4-yl)-piperazin-1-yl]-ethanoneHCID 574368002-((1-(4-Methoxy-2,6-dimethylphenylsulfonyl)piperidin-2-yl)methoxy)acetic acid

生成物 1

HCID 249455732-((1-(4-Methoxy-2,6-dimethylphenylsulfonyl)piperidin-2-yl)methoxy)-1-(4-(1-methyl-piperidin-4-yl)piperazin-1-yl)ethanone dihydrochloride

試薬・触媒・溶媒 4

HCID 180Acetone触媒HCID 3283Diethyl Ether溶媒HCID 6344Dichloromethane溶媒2 回HCID 225585302-Butanone ethanol溶媒

実験手順

N,N′-Carbonyldiimidazole (272 mg, 1.696 mmol) was added to a solution of 2-((1-(4-methoxy-2,6-dimethylphenylsulfonyl)piperidin-2-yl)methoxy)acetic acid (600 mg, 1.615 mmol) in dichloromethane (15 ml), and the mixture was stirred for 1 h at room temperature. A solution of 1-(1-methylpiperidin-4-yl)piperazine (293 mg, 1.615 mmol) in dichloromethane (5 ml) was then added, and the reaction mixture was stirred for 15 h at room temperature. Saturated sodium hydrogen carbonate solution (20 ml) was then added to the reaction mixture, and then the aqueous phase was extracted with dichloromethane (2×20 ml). The combined organic phases were extracted with saturated sodium chloride solution (20 ml), dried over sodium sulfate and concentrated in vacuo. The crude product was purified by flash chromatography using dichloromethane/methanol (5:1). 2-((1-(4-methoxy-2,6-dimethylphenylsulfonyl)piperidin-2-yl)methoxy)-1-(4-(1-methylpiperidin-4-yl)piperazin-1-yl)ethanone (590 mg, 1.105 mmol) was dissolved in methyl ethyl ketone/ethanol (1:1) (20 ml) [plus a few drops of acetone], and chlorotrimethylsilane (168 μl, 1.326 mmol) was added slowly. Diethyl ether (20 ml) was then added, and the mixture was stirred for 1 h at 0° C. The resulting precipitate was filtered off, dried with the exclusion of air and washed with diethyl ether.

後処理

  1. stirringthe reaction mixture was stirred for 15 h at room temperature
  2. extractionthe aqueous phase was extracted with dichloromethane (2×20 ml)
  3. extractionThe combined organic phases were extracted with saturated sodium chloride solution (20 ml)
  4. dry with materialdried over sodium sulfate
  5. concentrationconcentrated in vacuo
  6. customThe crude product was purified by flash chromatography
  7. additionwas added slowly
  8. stirringthe mixture was stirred for 1 h at 0° C
  9. filtrationThe resulting precipitate was filtered off
  10. customdried with the exclusion of air
  11. washwashed with diethyl ether

出典と根拠

ORDレコード
ord-5d2629f9f2c7402897e5880385145893
出典データセット
uspto-grants-2013_05
特許番号
US08435978B2

関連ノート

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