Tetrahydrofuran → 4-[1-Phenyl-1-(1-methylimidazol-4-yl)methylene]piperidine-1-carboxylic acid tert-butyl ester
Reaction equation
[C:1]([O:5][C:6]([N:8]1[CH2:13][CH2:12][CH2:11][CH2:10][CH2:9]1)=[O:7])([CH3:4])([CH3:3])[CH3:2].C([Sn](CCCC)(CCCC)[C:19]1[N:20]=[CH:21][N:22]([CH3:24])[CH:23]=1)CCC.O1C=[CH:36][CH:35]=[C:34]1P(C1OC=CC=1)C1OC=CC=1.[F-].[K+].[CH2:51]1[CH2:55]O[CH2:53][CH2:52]1>>[C:1]([O:5][C:6]([N:8]1[CH2:13][CH2:12][C:11](=[C:53]([C:52]2[CH:36]=[CH:35][CH:34]=[CH:55][CH:51]=2)[C:19]2[N:20]=[CH:21][N:22]([CH3:24])[CH:23]=2)[CH2:10][CH2:9]1)=[O:7])([CH3:4])([CH3:2])[CH3:3]Participants
Reactant 5
Product 1
Conditions
- Temperature
- 70 °C
Procedure
A mixture of 4-(1-phenyl-1-iodo)methylene)-piperidine-1-carboxylic acid tert-butyl ester (0.112 g, 0.280 mmol), 4-tri-n-butylstannyl-1-methylimidazole (0.181 g, 0.486 mmol) Pd2(dba)3 (0.013 mg, 0.014 mmol) and tri-(2-furyl)phosphine (0.007 g, 0.031 mmol) in THF (4 mL) was heated at 70° C. in a sealed tube under Ar for 12 h. The mixture was cooled to rt, aqueous KF was added and the mixture was allowed to stir for 2 h. The resulting mixture was extracted with EtOAc (×3) and the combined organic layers were washed (H2O, brine), dried (Na2SO4) and concentrated in vacuo. The residue was purified by preparative HPLC (NH4OAc) to give the title compound (0.047 g, 47%) as an oil which was slightly contaminated with the starting stannane. This material was used in the following step without further purification.
Workup
- temperatureThe mixture was cooled to rt
- extractionThe resulting mixture was extracted with EtOAc (×3)
- washthe combined organic layers were washed (H2O, brine)
- dry with materialdried (Na2SO4)
- concentrationconcentrated in vacuo
- customThe residue was purified by preparative HPLC (NH4OAc)
Sources & evidence
- ORD record
- ord-003ab3a6b67a4b6abcc9386e3e892f51
- Source dataset
- uspto-grants-2008_03
- Patent number
- US07348337B2
Reaction notes
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