3-Chlorobenzenesulphonyl chloride → {4-[1-(3-Chloro-benzenesulfonyl)-piperidin-4-yl]-6-fluoro-naphthalen-2-yl}-acetic acid methyl ester

HRID 2363838노트

반응식

HRID 2363838 반응식
C(N(C(C)C)CC)(C)C.FC(F)(F)C(O)=O.[CH3:17][O:18][C:19](=[O:38])[CH2:20][C:21]1[CH:30]=[C:29]([CH:31]2[CH2:36][CH2:35][NH:34][CH2:33][CH2:32]2)[C:28]2[C:23](=[CH:24][CH:25]=[C:26]([F:37])[CH:27]=2)[CH:22]=1.[Cl:39][C:40]1[CH:41]=[C:42]([S:46](Cl)(=[O:48])=[O:47])[CH:43]=[CH:44][CH:45]=1>O1CCCC1>[CH3:17][O:18][C:19](=[O:38])[CH2:20][C:21]1[CH:30]=[C:29]([CH:31]2[CH2:36][CH2:35][N:34]([S:46]([C:42]3[CH:43]=[CH:44][CH:45]=[C:40]([Cl:39])[CH:41]=3)(=[O:48])=[O:47])[CH2:33][CH2:32]2)[C:28]2[C:23](=[CH:24][CH:25]=[C:26]([F:37])[CH:27]=2)[CH:22]=1

참가 물질

5

반응물 3

HCID 179093-Chlorobenzenesulphonyl chlorideHCID 81531DiisopropylethylamineHCID 86686887HCID 86686887, 화합물

생성물 1

HCID 86686898{4-[1-(3-Chloro-benzenesulfonyl)-piperidin-4-yl]-6-fluoro-naphthalen-2-yl}-acetic acid methyl ester수율 56.6%

시약·촉매·용매 1

HCID 8028Tetrahydrofuran용매

실험 절차

Diisopropylethylamine (0.3 mL, 1.7 mmol) was added at 0° C. to a solution of (6-fluoro-4-piperidin-4-yl-naphthalen-2-yl)-acetic acid methyl ester trifluoroacetate salt (which may be prepared as described above; 150 mg, 0.36 mmol) in tetrahydrofuran (5 mL), and the mixture was stirred at room temperature for 30 min. 3-Chlorobenzenesulfonyl chloride (available from Sigma-Aldrich; 110 mg, 0.52 mmol) was added and the mixture was stirred at room temperature for 16 h. The solvent was evaporated under reduced pressure. Ethyl acetate was added and the mixture was washed with aqueous NaHCO3 (5 mL) and water (5 mL). The organic layer was dried over Na2SO4, filtered, and evaporated under reduced pressure. The residue was purified by chromatography on silica gel using a Biotage purification system, eluting with 10% ethyl acetate/hexanes, to give {4-[1-(3-chloro-benzenesulfonyl)-piperidin-4-yl]-6-fluoro-naphthalen-2-yl}-acetic acid methyl ester (97 mg, 56%) as a white solid. MS cald. for C24H24ClFNO4S [(M+H)+]: 476, obsd. 476.4.

후처리

  1. stirringthe mixture was stirred at room temperature for 16 h
  2. customThe solvent was evaporated under reduced pressure
  3. additionEthyl acetate was added
  4. washthe mixture was washed with aqueous NaHCO3 (5 mL) and water (5 mL)
  5. dry with materialThe organic layer was dried over Na2SO4
  6. filtrationfiltered
  7. customevaporated under reduced pressure
  8. customThe residue was purified by chromatography on silica gel using
  9. customa Biotage purification system
  10. washeluting with 10% ethyl acetate/hexanes

출처 및 근거

ORD 기록
ord-748e665ee4eb4a56b5b9bf9a249454f4
출처 데이터셋
uspto-grants-2014_04
특허 번호
US08691993B2

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