Sodium Carbonate → Tert-butyl 4-(4-amino-3-methoxyphenyl)piperidine-1-carboxylate

HRID 419410Notes

Reaction equation

HRID 419410 reaction equation
Cl[C:2]1[CH:3]=[CH:4][C:5]([N+:10]([O-])=O)=[C:6]([O:8][CH3:9])[CH:7]=1.CC1(C)C(C)(C)OB([C:21]2[CH2:22][CH2:23][N:24]([C:27]([O:29][C:30]([CH3:33])([CH3:32])[CH3:31])=[O:28])[CH2:25][CH:26]=2)O1.C([O-])([O-])=O.[Na+].[Na+]>O1CCOCC1.O.CCO.Cl[Pd](Cl)([P](C1C=CC=CC=1)(C1C=CC=CC=1)C1C=CC=CC=1)[P](C1C=CC=CC=1)(C1C=CC=CC=1)C1C=CC=CC=1>[NH2:10][C:5]1[CH:4]=[CH:3][C:2]([CH:21]2[CH2:26][CH2:25][N:24]([C:27]([O:29][C:30]([CH3:33])([CH3:32])[CH3:31])=[O:28])[CH2:23][CH2:22]2)=[CH:7][C:6]=1[O:8][CH3:9]

Participants

8

Reactant 3

HCID 10340Sodium CarbonateHCID 811105-Chloro-2-nitroanisoleHCID 4642098Tert-butyl 4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1,2,3,6-tetrahydropyridine-1-carboxylate

Product 1

HCID 57416157Tert-butyl 4-(4-amino-3-methoxyphenyl)piperidine-1-carboxylateYield 81%

Reagents, catalysts & solvents 4

HCID 178418476HCID 178418476, compoundCatalystHCID 702EthanolSolventHCID 962WaterSolventHCID 312751,4-DioxaneSolvent

Conditions

Temperature
120 °C

Procedure

5-chloro-2-nitroanisole (0.094 g, 0.50 mmol), 1,1-dimethylethyl 4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-3,6-dihydro-1(2H)-pyridinecarboxylate (0.19 g, 0.60 mmol), Na2CO3 (0.16 g, 1.5 mmol) and bis(triphenylphosphine)palladium(II) chloride (0.019 g, 0.030 mmol) in dioxane (3 mL) and H2O (1.5 mL) was degassed for 30 min. The mixture was heated at 120° C. for 20 min in the microwave. Upon completion by TLC, the reaction was placed under H2 (1 atm.). The mixture was transferred to a separate flask and diluted with EtOH and subsequently stirred under H2 (1 atm.) overnight. Upon completion by TLC, the reaction was filtered through Celite®, washed with EtOAc, dried (MgSO4), concentrated and purified by flash chromatography to provide the title compound of step A (0.12 g, 0.40 mmol, 81%). 1H NMR (400 MHz, CDCl3) δ ppm 1.48 (s, 9H), 1.52-1.64 (m, 2H), 1.79 (d, J=12.8 Hz, 2H), 2.54 (tt, J=12.1, 3.5 Hz, 1H), 2.77 (t, J=11.9 Hz, 2H), 3.65 (d, J=2.6 Hz, 1H), 3.70 (d, J=6.2 Hz, 1H), 3.83 (s, 3H), 4.22 (br. s., 2H), 6.60-6.66 (m, 3H).

Workup

  1. customThe mixture was transferred to a separate flask
  2. filtrationUpon completion by TLC, the reaction was filtered through Celite®
  3. washwashed with EtOAc
  4. dry with materialdried (MgSO4)
  5. concentrationconcentrated
  6. custompurified by flash chromatography

Sources & evidence

ORD record
ord-672c1d34f8354a26a6bdbef688e06828
Source dataset
uspto-grants-2012_01
Patent number
US08093239B2

Reaction notes

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