Potassium Hydroxide → 4-(2,5-Dimethyl-4-nitrophenyl)-1-(4-methoxybenzyl)piperidin-2-one

HRID 1897691Notes

Reaction equation

HRID 1897691 reaction equation
[CH3:1][C:2]1[CH:7]=[C:6]([N+:8]([O-:10])=[O:9])[C:5]([CH3:11])=[CH:4][C:3]=1B1OC(C)(C)C(C)(C)O1.[CH3:21][O:22][C:23]1[CH:36]=[CH:35][C:26]([CH2:27][N:28]2[CH2:33][CH2:32][CH:31]=[CH:30][C:29]2=[O:34])=[CH:25][CH:24]=1.[OH-].[K+]>C1CC=CCCC=C1.C1CC=CCCC=C1.[Cl-].[Cl-].[Rh].[Rh].O1CCOCC1>[CH3:1][C:2]1[CH:7]=[C:6]([N+:8]([O-:10])=[O:9])[C:5]([CH3:11])=[CH:4][C:3]=1[CH:31]1[CH2:32][CH2:33][N:28]([CH2:27][C:26]2[CH:25]=[CH:24][C:23]([O:22][CH3:21])=[CH:36][CH:35]=2)[C:29](=[O:34])[CH2:30]1

Participants

6

Reactant 3

HCID 14797Potassium HydroxideHCID 145643581-(4-Methoxybenzyl)-5,6-dihydropyridin-2(1H)-oneHCID 671555522-(2,5-Dimethyl-4-nitrophenyl)-4,4,5,5-tetramethyl-1,3,2-dioxaborolane

Product 1

HCID 671553414-(2,5-Dimethyl-4-nitrophenyl)-1-(4-methoxybenzyl)piperidin-2-one

Reagents, catalysts & solvents 2

HCID 6436379Rhodium, di-mu-chlorobis((1,2,5,6-eta)-1,5-cyclooctadiene)di-CatalystHCID 312751,4-DioxaneSolvent

Conditions

Temperature
100 °C

Procedure

In a 5 mL microwave reaction tube was added 2-(2,5-dimethyl-4-nitrophenyl)-4,4,5,5-tetramethyl-1,3,2-dioxaborolane (143 mg, 0.516 mmol, prepared from 1-bromo-2,5-dimethyl-4-nitrobenzene by standard protocol), 1-(4-methoxybenzyl)-5,6-dihydropyridin-2(1H)-one (56 mg, 0.26 mmol, prepared by following a similar procedure as reported by Lerchner etc. in Chem. Eur. J. 2006, 12, 8208), chloro(1,5-cyclooctadiene)rhodium (I) dimer (13 mg, 0.026 mmol), KOH (0.13 mL 1N aqueous solution) and dioxane (1.2 mL). The tube was degassed, filled with N2 and sealed. The reaction tube was then heated to 100° C. in a microwave reactor for 10 min. After the reaction tube was opened, the mixture was treated with saturated NH4Cl aqueous solution (3 mL) and extracted with EtOAc (3×4 mL). The organic layers were combined and concentrated. The residue was purified by flash column chromatography (silica gel, gradient 0%-70% EtOAc/hexane), to provide 4-(2,5-dimethyl-4-nitrophenyl)-1-(4-methoxybenzyl)piperidin-2-one. ESMS m/z 369.2 (M+H+).

Workup

  1. customprepared
  2. customThe tube was degassed
  3. additionfilled with N2
  4. customsealed
  5. additionthe mixture was treated with saturated NH4Cl aqueous solution (3 mL)
  6. extractionextracted with EtOAc (3×4 mL)
  7. concentrationconcentrated
  8. customThe residue was purified by flash column chromatography (silica gel, gradient 0%-70% EtOAc/hexane)

Sources & evidence

ORD record
ord-cfc9811cd44a4b1fb100c31b886ee20c
Source dataset
uspto-grants-2013_08
Patent number
US08519129B2

Reaction notes

Loading…