Chlorotrimethylsilane → 1-(4-Hydroxy-4-(pyridin-3-yl)piperidin-1-yl)-2-((1-(4-methoxy-2,6-dimethylphenylsulfonyl)pyrrolidin-2-yl)methoxy)ethanone hydrochloride

HRID 2041090노트

반응식

HRID 2041090 반응식
COC1C=C(C)C(S(N2CCCC2COCC(O)=O)(=O)=O)=C(C)C=1.N1C=CC=C(C2(O)CCNCC2)C=1.C(=O)(O)[O-].[Na+].[OH:43][C:44]1([C:73]2[CH:74]=[N:75][CH:76]=[CH:77][CH:78]=2)[CH2:49][CH2:48][N:47]([C:50](=[O:72])[CH2:51][O:52][CH2:53][CH:54]2[CH2:58][CH2:57][CH2:56][N:55]2[S:59]([C:62]2[C:67]([CH3:68])=[CH:66][C:65]([O:69][CH3:70])=[CH:64][C:63]=2[CH3:71])(=[O:61])=[O:60])[CH2:46][CH2:45]1.[Cl:79][Si](C)(C)C>C(Cl)Cl.C(C(C)=O)C.C(OCC)C.C(OCC)C>[ClH:79].[OH:43][C:44]1([C:73]2[CH:74]=[N:75][CH:76]=[CH:77][CH:78]=2)[CH2:45][CH2:46][N:47]([C:50](=[O:72])[CH2:51][O:52][CH2:53][CH:54]2[CH2:58][CH2:57][CH2:56][N:55]2[S:59]([C:62]2[C:67]([CH3:68])=[CH:66][C:65]([O:69][CH3:70])=[CH:64][C:63]=2[CH3:71])(=[O:60])=[O:61])[CH2:48][CH2:49]1

참가 물질

9

반응물 5

HCID 6397ChlorotrimethylsilaneHCID 516892Sodium BicarbonateHCID 49891674-(Pyridin-3-yl)piperidin-4-olHCID 59746454HCID 59746454, 화합물HCID 598200831-(4-Hydroxy-4-(pyridin-3-yl)piperidin-1-yl)-2-((1-(4-methoxy-2,6-dimethylphenylsulfonyl)pyrrolidin-2-yl)methoxy)ethanone

생성물 1

HCID 693243031-(4-Hydroxy-4-(pyridin-3-yl)piperidin-1-yl)-2-((1-(4-methoxy-2,6-dimethylphenylsulfonyl)pyrrolidin-2-yl)methoxy)ethanone hydrochloride

시약·촉매·용매 3

HCID 3283Diethyl Ether용매HCID 6344Dichloromethane용매2회HCID 19800284Diethyl ether 2-butanone용매

실험 절차

N,N′-Carbonyldiimidazole (71 mg, 0.441 mmol) was added to a solution of 2-((1-(4-methoxy-2,6-dimethylphenylsulfonyl)pyrrolidin-2-yl)methoxy)acetic acid (acid unit S27) (150 mg, 0.420 mmol) in methylene chloride (7 ml) and the mixture was stirred for 1 h at room temperature. A solution of 4-(pyridin-3-yl)piperidin-4-ol (A2) (74 mg, 0.420 mmol) in methylene chloride (3 ml) was subsequently added and the reaction mixture was stirred for 15 h at room temperature. Thereafter, saturated sodium bicarbonate solution (10 ml) was added to the reaction mixture and the aqueous phase was subsequently extracted with methylene chloride (2×10 ml). The combined organic phases were extracted with saturated sodium chloride solution (10 ml), dried with sodium sulfate and concentrated in vacuo. The crude product was purified by flash chromatography with ethyl acetate/methanol/hexane (10:1:1). 1-(4-Hydroxy-4-(pyridin-3-yl)piperidin-1-yl)-2-((1-(4-methoxy-2,6-dimethylphenylsulfonyl)pyrrolidin-2-yl)methoxy)ethanone (160 mg, 0.309 mmol) was dissolved in methyl ethyl ketone/diethyl ether (1:1; 5 ml), and chlorotrimethylsilane (59 μl, 0.464 mmol) was slowly added. Diethyl ether (10 ml) was subsequently added and the mixture was stirred for 1 h at 0° C. The precipitate formed was filtered off, dried with exclusion of air and washed with diethyl ether.

후처리

  1. stirringthe reaction mixture was stirred for 15 h at room temperature
  2. extractionthe aqueous phase was subsequently extracted with methylene chloride (2×10 ml)
  3. extractionThe combined organic phases were extracted with saturated sodium chloride solution (10 ml)
  4. dry with materialdried with sodium sulfate
  5. concentrationconcentrated in vacuo
  6. customThe crude product was purified by flash chromatography with ethyl acetate/methanol/hexane (10:1:1)
  7. stirringthe mixture was stirred for 1 h at 0° C
  8. customThe precipitate formed
  9. filtrationwas filtered off
  10. customdried with exclusion of air
  11. washwashed with diethyl ether

출처 및 근거

ORD 기록
ord-cd777d83155743dc9e78cef61412562d
출처 데이터셋
uspto-grants-2013_11
특허 번호
US08580965B2

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