Piperidine → HCID 67529104, compound

HRID 219783Notes

Reaction equation

HRID 219783 reaction equation
Br[C:2]1[CH:11]=[CH:10][C:5]([C:6]([O:8][CH3:9])=[O:7])=[CH:4][C:3]=1[CH3:12].C([O-])([O-])=O.[Cs+].[Cs+].[NH:19]1[CH2:24][CH2:23][CH2:22][CH2:21][CH2:20]1>O1CCOCC1.C([O-])(=O)C.[Pd+2].C([O-])(=O)C.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>[CH3:12][C:3]1[CH:4]=[C:5]([CH:10]=[CH:11][C:2]=1[N:19]1[CH2:24][CH2:23][CH2:22][CH2:21][CH2:20]1)[C:6]([O:8][CH3:9])=[O:7]

Participants

7

Reactant 3

HCID 8082PiperidineHCID 10796Cesium carbonateHCID 3294148Methyl 4-bromo-3-methylbenzoate

Product 1

HCID 67529104HCID 67529104, compoundYield 96.3%

Reagents, catalysts & solvents 3

HCID 167845palladium(II) acetateCatalystHCID 634876Binap, (A+-)-CatalystHCID 312751,4-DioxaneSolvent

Procedure

To a stirred solution of methyl 4-bromo-3-methylbenzoate (ABCR, 5 g, 21.8 mmol) in dry 1,4-dioxane (100 mL), were added dry Cs2CO3 (10.65 g, 32.7 mmol) and piperidine (2.2 g, 26 mmol). The mixture was degassed with N2 for 10 min. BINAP (0.67 g, 1.1 mmol) and palladium(II)acetate (0.24 g, 1.1 mmol) were added under N2 and the resulting mixture was refluxed for 15 h. The reaction mixture was filtered through a pad of celite and the filtrate was evaporated. The crude product was purified by flash chromatography, affording the title product as a off-white solid (4.9 g, 96%). 1H NMR (CDCl3, 400 MHz) δ 7.82-7.84 (m, 2H), 6.97-6.99 (d, 1H), 3.92 (s, 3H), 2.90-2.93 (m, 4H), 1.67-1.76 (m, 4H), 1.62-1.63 (m, 2H). LC/MS (Method A): 233.9 (M+H)+. HPLC (Method B) Rt 4.18 min (Purity: 95.4%).

Workup

  1. customThe mixture was degassed with N2 for 10 min
  2. temperaturethe resulting mixture was refluxed for 15 h
  3. filtrationThe reaction mixture was filtered through a pad of celite
  4. customthe filtrate was evaporated
  5. customThe crude product was purified by flash chromatography

Sources & evidence

ORD record
ord-7321dd151456407d8634d6d82709b9ed
Source dataset
uspto-grants-2012_06
Patent number
US08202865B2

Reaction notes

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