반응 #43516

반응 방정식

4-(2-tri-iso-propylsilanylsulfanyl-phenyl)-piperidine-1-carboxylic acid tert-butyl ester

1-iodo-4-trifluoromethyl-benzene

potassium tert-butoxide

tetra-n-butyl ammonium fluoride

→

4-[2-(4-trifluoromethyl-phenylsulfanyl)-phenyl]-piperidine-1-carboxylic acid tert-butyl ester

수율 59.2%

용매

heptane

ethyl acetate

반응 조건

후처리

1. 1
   workup.DISSOLUTIONwas dissolved
2. 2
   기타in dry
3. 3
   기타degassed toluene (0.3 mL)
4. 4
   workup.DISSOLUTIONPd2dba3 (1 mg) and DPEphos (1 mg) dissolved in dry toluene (0.2 mL)
5. 5
   workup.ADDITIONwere added
6. 6
   여과The solution was filtered
7. 7
   기타the solvent was evaporated off
8. 8
   기타The crude product was purified by chromatography on silica gel (eluent

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%.

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