(Diethylamino)sulfur trifluoride → Methyl 4-[3-(3-chloro-6-methoxyquinolin-4-yl)-3-(r,s)-fluoropropyl]-1-[2-(2,5-difluorophenylthio)ethyl]piperidine-4-carboxylate

HRID 395010노트

반응식

HRID 395010 반응식
C(N(S(F)(F)[F:7])CC)C.[Cl:10][C:11]1[CH:12]=[N:13][C:14]2[C:19]([C:20]=1[CH:21](O)[CH2:22][CH2:23][C:24]1([C:41]([O:43][CH3:44])=[O:42])[CH2:29][CH2:28][N:27]([CH2:30][CH2:31][S:32][C:33]3[CH:38]=[C:37]([F:39])[CH:36]=[CH:35][C:34]=3[F:40])[CH2:26][CH2:25]1)=[CH:18][C:17]([O:46][CH3:47])=[CH:16][CH:15]=2.C(=O)([O-])O.[Na+]>ClCCl>[Cl:10][C:11]1[CH:12]=[N:13][C:14]2[C:19]([C:20]=1[CH:21]([F:7])[CH2:22][CH2:23][C:24]1([C:41]([O:43][CH3:44])=[O:42])[CH2:25][CH2:26][N:27]([CH2:30][CH2:31][S:32][C:33]3[CH:38]=[C:37]([F:39])[CH:36]=[CH:35][C:34]=3[F:40])[CH2:28][CH2:29]1)=[CH:18][C:17]([O:46][CH3:47])=[CH:16][CH:15]=2

참가 물질

5

반응물 3

HCID 123472(Diethylamino)sulfur trifluorideHCID 516892Sodium BicarbonateHCID 22469786Methyl 4-[3-(3-chloro-6-methoxyquinolin-4-yl)-3-(r,s)-hydroxypropyl]-1-[2-(2,5-difluorophenylthio)ethyl]piperidine-4-carboxylate

생성물 1

HCID 22468945Methyl 4-[3-(3-chloro-6-methoxyquinolin-4-yl)-3-(r,s)-fluoropropyl]-1-[2-(2,5-difluorophenylthio)ethyl]piperidine-4-carboxylate

시약·촉매·용매 1

HCID 6344Dichloromethane용매

반응 조건

온도
5 °C

실험 절차

0.1 cm3 of diethylaminosulfur trifluoride was added to a solution of 0.25 g of methyl 4-[3-(3-chloro-6-methoxyquinolin-4-yl)-3-(R,S)-hydroxypropyl]-1-[2-(2,5-difluorophenylthio)ethyl]piperidine-4-carboxylate in 10 cm3 of dichloromethane, with stirring and under an inert atmosphere, at a temperature in the region of 5° C. After stirring for 7 hours at a temperature in the region of 20° C., saturated sodium hydrogen carbonate solution was added to the reaction mixture. The aqueous phase was extracted with dichloromethane. The organic phase was dried over magnesium sulfate, filtered and then concentrated to dryness under reduced pressure (2 kPa) at a temperature in the region of 40° C. The residue obtained was purified by chromatography under atmospheric pressure, on a column of silica gel (particle size 70-200μ; mass: 15 g), eluting with 60 cm3 of dichloromethane, then with 45 cm3 of a mixture of ethyl acetate/dichloromethane (1/9 by volume), then with 30 cm3 of a mixture of ethyl acetate/dichloromethane (2/8 by volume) and then with 210 cm3 of a mixture of ethyl acetate/dichloromethane (3/7 by volume) and then with ethyl acetate. Fractions 24 to 26 were combined and then concentrated to dryness according to the same conditions as above. 0.08 g of methyl 4-[3-(3-chloro-6-methoxyquinolin-4-yl)-3-(R,S)-fluoropropyl]-1-[2-(2,5-difluorophenylthio)ethyl]piperidine-4-carboxylate was obtained in the form of a thick yellow oil.

후처리

  1. additionwas added to the reaction mixture
  2. extractionThe aqueous phase was extracted with dichloromethane
  3. dry with materialThe organic phase was dried over magnesium sulfate
  4. filtrationfiltered
  5. concentrationconcentrated to dryness under reduced pressure (2 kPa) at a temperature in the region of 40° C
  6. customThe residue obtained
  7. customwas purified by chromatography under atmospheric pressure, on a column of silica gel (particle size 70-200μ; mass: 15 g)
  8. washeluting with 60 cm3 of dichloromethane
  9. concentrationconcentrated to dryness

출처 및 근거

ORD 기록
ord-bcc25d0c2d8b419ba0b44c2e743ae50b
출처 데이터셋
uspto-grants-2003_08
특허 번호
US06603005B2

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