Indole → 4-[2-(1H-indol-3-ylsulfanyl)-phenyl]-piperidine-1-carboxylic acid tert-butyl ester

HRID 2244046

반응식

HRID 2244046 반응식
[C:1]([O:5][C:6]([N:8]1[CH2:13][CH2:12][CH:11]([C:14]2[CH:19]=[CH:18][CH:17]=[CH:16][C:15]=2[S:20][Si](C(C)C)(C(C)C)C(C)C)[CH2:10][CH2:9]1)=[O:7])([CH3:4])([CH3:3])[CH3:2].O.O.[F-].C([N+:38]([CH2:47][CH2:48][CH2:49][CH3:50])([CH2:43][CH2:44][CH2:45][CH3:46])CCCC)CCC.ClN1C(=O)CCC1=O.N1C2C(=CC=CC=2)C=C1.C([O-])(O)=O.[Na+]>C1COCC1.ClCCCl>[C:1]([O:5][C:6]([N:8]1[CH2:13][CH2:12][CH:11]([C:14]2[CH:19]=[CH:18][CH:17]=[CH:16][C:15]=2[S:20][C:48]2[C:49]3[C:43](=[CH:44][CH:45]=[CH:46][CH:50]=3)[NH:38][CH:47]=2)[CH2:10][CH2:9]1)=[O:7])([CH3:4])([CH3:2])[CH3:3]

참가 물질

8

반응물 5

HCID 798IndoleHCID 31398ChlorosuccinimideHCID 516892Sodium BicarbonateHCID 22343550Tetrabutylammonium fluoride dihydrateHCID 686357834-(2-Triisopropylsilanylsulfanyl-phenyl)-piperidine-1-carboxylic acid tert-butyl ester

생성물 1

HCID 686342064-[2-(1H-indol-3-ylsulfanyl)-phenyl]-piperidine-1-carboxylic acid tert-butyl ester수율 44%

시약·촉매·용매 2

HCID 111,2-Dichloroethane용매HCID 8028Tetrahydrofuran용매3회

반응 조건

온도
0 °C

실험 절차

1.58 g 4-(2-Triisopropylsilanylsulfanyl-phenyl)-piperidine-1-carboxylic acid tert-butyl ester (3.51 mmol) in 10 mL THF was added to 1.21 g tetrabutylammonium fluoride dihydrate (3.85 mmol) in 5 mL THF at 0° C. The reaction mixture was stirred 1 hour at 0° C., filtered through a plug of silica (eluted with EtOAc/heptane 1:1) and concentrated in vacuo. The residue was redissolved in 14 mL THF. 2 mL of this solution (≈0.5 mmol) was added to 67 mg N-chloro succinimide (0.50 mmol) in 2 mL 1,2-dichloro-ethane at 0° C. The reaction mixture was stirred 30 minutes at room temperature. The resulting solution was added to 90 mg indole (0.75 mmol) in 2 mL THF at 0° C. The reaction mixture was stirred 2 hour at 0° C., poured into 20 mL saturated NaHCO3 and extracted with ethyl acetate (2×50 mL). The combined organic phases were washed with brine (20 mL), dried with MgSO4 and concentrated in vacuo. The residue was purified by flash chromatography (silica gel; ethyl acetate/heptane) to give 89 mg 4-[2-(1H-indol-3-ylsulfanyl)-phenyl]-piperidine-1-carboxylic acid tert-butyl ester (0.22 mmol, ≈44%). 2 mL diethyl ether saturated with HCl was added to 4-[2-(1H-indol-3-ylsulfanyl)-phenyl]-piperidine-1-carboxylic acid tert-butyl ester and stirred over night at room temperature. The reaction mixture was neutralized with saturated NaHCO3 and extracted with ethyl acetate (2×50 mL). The combined organic phases were washed with brine (20 mL), dried with MgSO4 and concentrated in vacuo. 3-(2-piperidin-4-yl-phenylsulfanyl)-1H-indole was isolated after preparative HPLC.

후처리

  1. filtrationfiltered through a plug of silica (eluted with EtOAc/heptane 1:1)
  2. concentrationconcentrated in vacuo
  3. dissolutionThe residue was redissolved in 14 mL THF
  4. stirringThe reaction mixture was stirred 30 minutes at room temperature
  5. stirringThe reaction mixture was stirred 2 hour at 0° C.
  6. extractionextracted with ethyl acetate (2×50 mL)
  7. washThe combined organic phases were washed with brine (20 mL)
  8. dry with materialdried with MgSO4
  9. concentrationconcentrated in vacuo
  10. customThe residue was purified by flash chromatography (silica gel; ethyl acetate/heptane)

출처 및 근거

ORD 기록
ord-0e10bbcad95143de804e250679ba5e29
출처 데이터셋
uspto-grants-2010_03
특허 번호
US07678800B2

연결된 노트

불러오는 중…