Benzene, 1-iodo-4-(trifluoromethyl)- → 4-[2-(4-Trifluoromethyl-phenylsulfanyl)-phenyl]-piperidine-1-carboxylic acid tert-butyl ester

HRID 15238

반응식

HRID 15238 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].I[C:32]1[CH:37]=[CH:36][C:35]([C:38]([F:41])([F:40])[F:39])=[CH:34][CH:33]=1.CC(C)([O-])C.[K+].[F-].C([N+](CCCC)(CCCC)CCCC)CCC>CCCCCCC.C(OCC)(=O)C>[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:32]2[CH:37]=[CH:36][C:35]([C:38]([F:41])([F:40])[F:39])=[CH:34][CH:33]=2)[CH2:10][CH2:9]1)=[O:7])([CH3:2])([CH3:3])[CH3:4]

참가 물질

7

반응물 4

HCID 67993Benzene, 1-iodo-4-(trifluoromethyl)-HCID 2724141Tetrabutylammonium FluorideHCID 23665647Potassium tert-butoxideHCID 686357834-(2-Triisopropylsilanylsulfanyl-phenyl)-piperidine-1-carboxylic acid tert-butyl ester

생성물 1

HCID 686811394-[2-(4-Trifluoromethyl-phenylsulfanyl)-phenyl]-piperidine-1-carboxylic acid tert-butyl ester수율 59.2%

시약·촉매·용매 2

HCID 8857Ethyl Acetate용매HCID 8900Heptane용매

반응 조건

온도
110 °C

실험 절차

A mixture of 4-(2-tri-iso-propylsilanylsulfanyl-phenyl)-piperidine-1-carboxylic acid tert-butyl ester (38 mg, 0.085 mmol) and 1-iodo-4-trifluoromethyl-benzene (23 mg, 0.085 mmol) was dissolved in dry degassed toluene (0.3 mL). Pd2dba3 (1 mg) and DPEphos (1 mg) dissolved in dry toluene (0.2 mL) were added. To this solution were added potassium tert-butoxide (10 mg) and tetra-n-butyl ammonium fluoride (TBAF, 1M in TBF, 0.1 mL, 0.1 mmol) and the reaction mixture was stirred at 110° C. for 1 h under argon. The solution was filtered and the solvent was evaporated off. The crude product was purified by chromatography on silica gel (eluent: An increasing amount (0-100%) of ethyl acetate in heptane) to produce 4-[2-(4-trifluoromethyl-phenylsulfanyl)-phenyl]-piperidine-1-carboxylic acid tert-butyl ester (3a1) as a clear oil (22 mg, 59% yield). This material was dissolved in methanol (1 mL) and hydrogen chloride in diethyl ether (2M, 1 mL) was added and the solution was stirred overnight at rt. The solvent was evaporated of and the crude product was purified by BPLC (containing 0.1% TFA in the standard eluent) to produce 4-[2-(4-trifluoromethyl-phenylsulfanyl)-phenyl]-piperidine 3a1 as the trifluoro-acetic acid salt. Yield: 3.2 mg (8% overall). LC/TOF (m/z) 338.0 (MH+); RT=2.29 min; purity (UV, ELSD): 98.3%, 97.1%.

후처리

  1. dissolutionwas dissolved
  2. customin dry
  3. customdegassed toluene (0.3 mL)
  4. dissolutionPd2dba3 (1 mg) and DPEphos (1 mg) dissolved in dry toluene (0.2 mL)
  5. additionwere added
  6. filtrationThe solution was filtered
  7. customthe solvent was evaporated off
  8. customThe crude product was purified by chromatography on silica gel (eluent

출처 및 근거

ORD 기록
ord-e00a7c67eda048cfa266d1f33c8a8c27
출처 데이터셋
uspto-grants-2010_06
특허 번호
US07732463B2

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