Potassium Carbonate → Tert-butyl 4-[[4-(2,6-dimethylpyridin-4-yl)-2-methylphenyl]methyl]piperazine-1-carboxylate

HRID 2278274Notes

Reaction equation

HRID 2278274 reaction equation
Br[C:2]1[CH:7]=[CH:6][C:5]([CH2:8][N:9]2[CH2:14][CH2:13][N:12]([C:15]([O:17][C:18]([CH3:21])([CH3:20])[CH3:19])=[O:16])[CH2:11][CH2:10]2)=[C:4]([CH3:22])[CH:3]=1.[CH3:23][C:24]1[CH:29]=[C:28](B(O)O)[CH:27]=[C:26]([CH3:33])[N:25]=1.C(=O)([O-])[O-].[K+].[K+].O1CCOCC1>C1C=CC([P]([Pd]([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)[P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)=CC=1.O>[CH3:23][C:24]1[CH:29]=[C:28]([C:2]2[CH:7]=[CH:6][C:5]([CH2:8][N:9]3[CH2:14][CH2:13][N:12]([C:15]([O:17][C:18]([CH3:21])([CH3:20])[CH3:19])=[O:16])[CH2:11][CH2:10]3)=[C:4]([CH3:22])[CH:3]=2)[CH:27]=[C:26]([CH3:33])[N:25]=1

Participants

7

Reactant 4

HCID 11430Potassium CarbonateHCID 312751,4-DioxaneHCID 23546910(2,6-Dimethylpyridin-4-yl)boronic acidHCID 89676989Tert-butyl 4-[(4-bromo-2-methylphenyl)methyl]piperazine-1-carboxylate

Product 1

HCID 89677209Tert-butyl 4-[[4-(2,6-dimethylpyridin-4-yl)-2-methylphenyl]methyl]piperazine-1-carboxylateYield 89%

Reagents, catalysts & solvents 2

HCID 178418397HCID 178418397, compoundCatalystHCID 962WaterSolvent

Conditions

Temperature
75 °C

Procedure

A 25 mL round-bottom flask maintained with an inert atmosphere of nitrogen was charged with tert-butyl 4[(4-bromo-2-methylphenyl)methyl]piperazine-1-carboxylate (368 mg, 1.00 mmol, 1.00 equiv), (2,6-dimethylpyridin-4-yl)boronic acid (300 mg, 1.99 mmol, 1.99 equiv), Pd(PPh3)4 (116 mg, 0.100 mmol, 0.10 equiv), potassium carbonate (414 mg, 3.00 mmol, 3.01 equiv), dioxane (6 mL) and water (1 mL). The resulting solution was stirred overnight at 75° C. The reaction progress was monitored by LCMS. The reaction was then quenched by the addition of water (10 mL). The resulting solution was extracted with ethyl acetate (3×10 mL) and the organic layers were combined, washed with brine (2×10 mL), dried over anhydrous sodium sulfate and concentrated under reduced pressure. The residue was chromatographed on a silica gel column with ethyl acetate/petroleum ether (1/1) to yield 350 mg (89% yield) of tert-butyl 4-[[4-(2,6-dimethylpyridin-4-yl)-2-methylphenyl]methyl]piperazine-1-carboxylate as yellow oil. LCMS (ESI, m/z): 396 [M+H]+.

Workup

  1. temperatureA 25 mL round-bottom flask maintained with an inert atmosphere of nitrogen
  2. customThe reaction was then quenched by the addition of water (10 mL)
  3. extractionThe resulting solution was extracted with ethyl acetate (3×10 mL)
  4. washwashed with brine (2×10 mL)
  5. dry with materialdried over anhydrous sodium sulfate
  6. concentrationconcentrated under reduced pressure
  7. customThe residue was chromatographed on a silica gel column with ethyl acetate/petroleum ether (1/1)

Sources & evidence

ORD record
ord-509db5bbb63542acb1cf76088b7844c6
Source dataset
uspto-grants-2015_09
Patent number
US09133148B2

Reaction notes

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