Cesium carbonate → Methyl 3-(4-benzyloxycarbonylaminopiperidin-1-yl)benzoate

HRID 43824

Reaction equation

Br[C:2]1[CH:3]=[C:4]([CH:9]=[CH:10][CH:11]=1)[C:5]([O:7][CH3:8])=[O:6].C1C=CC(P(C2C(C3C(P(C4C=CC=CC=4)C4C=CC=CC=4)=CC=C4C=3C=CC=C4)=C3C(C=CC=C3)=CC=2)C2C=CC=CC=2)=CC=1.C(=O)([O-])[O-].[Cs+].[Cs+].[NH:64]1[CH2:69][CH2:68][CH:67]([NH:70][C:71](=[O:80])[O:72][CH2:73][C:74]2[CH:79]=[CH:78][CH:77]=[CH:76][CH:75]=2)[CH2:66][CH2:65]1>O1CCOCC1.CN(C)C=O.C(OCC)(=O)C.C([O-])(=O)C.[Pd+2].C([O-])(=O)C>[CH2:73]([O:72][C:71]([NH:70][CH:67]1[CH2:68][CH2:69][N:64]([C:2]2[CH:3]=[C:4]([CH:9]=[CH:10][CH:11]=2)[C:5]([O:7][CH3:8])=[O:6])[CH2:65][CH2:66]1)=[O:80])[C:74]1[CH:75]=[CH:76][CH:77]=[CH:78][CH:79]=1

Participants

Conditions

Temperature: 100 °C

Procedure

Methyl 3-bromobenzoate (230 mg, 1.07 mmol), palladium acetate (12 mg, 0.054 mmol), BINAP (133 mg, 0.214 mmol) and cesium carbonate (767 mg, 2.35 mmol) were added to a solution of benzyl piperidin-4-yl-carbamate obtained in Example (192b) (248 mg, 0.817 mmol) in 1,4-dioxane (10 mL) and N,N-dimethylformamide (2.5 mL), and the mixture was stirred at 100° C. for 20 hours. The reaction solution was cooled, diluted with ethyl acetate, and washed with brine. The organic layer was dried over magnesium sulfate, and then the solvent was evaporated under reduced pressure. The resulting residue was purified by silica gel column chromatography (elution solvent: hexane/ethyl acetate=3/1) to obtain 80 mg of the title compound as a colorless oily substance (20%).

Workup

temperatureThe reaction solution was cooled
washwashed with brine
dry with materialThe organic layer was dried over magnesium sulfate
customthe solvent was evaporated under reduced pressure
customThe resulting residue was purified by silica gel column chromatography (elution solvent: hexane/ethyl acetate=3/1)

Sources & evidence

ORD record: ord-2d442424469f4ef68a66b1df757b2b4d
Source dataset: uspto-grants-2013_09
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US08536197B2

Linked notes

Loading…