Cesium carbonate → 4-[1-(4-Tert-butyl-phenyl)-piperidin-4-yl]-butyric acid methyl ester

HRID 511173Notes

Reaction equation

HRID 511173 reaction equation
C1(P(C2C=CC=CC=2)C2C=CC3C(=CC=CC=3)C=2C2C3C(=CC=CC=3)C=CC=2P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.C(=O)([O-])[O-].[Cs+].[Cs+].Cl.[CH3:54][O:55][C:56](=[O:66])[CH2:57][CH2:58][CH2:59][CH:60]1[CH2:65][CH2:64][NH:63][CH2:62][CH2:61]1.Br[C:68]1[CH:73]=[CH:72][C:71]([C:74]([CH3:77])([CH3:76])[CH3:75])=[CH:70][CH:69]=1>O1CCOCC1.C(OCC)(=O)C.C([O-])(=O)C.[Pd+2].C([O-])(=O)C>[CH3:54][O:55][C:56](=[O:66])[CH2:57][CH2:58][CH2:59][CH:60]1[CH2:65][CH2:64][N:63]([C:68]2[CH:73]=[CH:72][C:71]([C:74]([CH3:77])([CH3:76])[CH3:75])=[CH:70][CH:69]=2)[CH2:62][CH2:61]1

Participants

8

Reactant 4

HCID 10796Cesium carbonate2×HCID 775951-Bromo-4-tert-butylbenzeneHCID 634876Binap, (A+-)-2×HCID 66672062Methyl 4-(piperidin-4-yl)butanoate hydrochloride

Product 1

HCID 585760674-[1-(4-Tert-butyl-phenyl)-piperidin-4-yl]-butyric acid methyl esterYield 60.5%

Reagents, catalysts & solvents 3

HCID 167845palladium(II) acetateCatalyst2×HCID 8857Ethyl AcetateSolventHCID 312751,4-DioxaneSolvent2×

Procedure

A mixture of palladium (II) acetate (63 mg; 0.28 mmol), (±)-2,2′-bis-diphenylphosphanyl-[1,1′]binaphthalenyl (258 mg; 0.41 mmol) and cesium carbonate (1.30 g; 4.00 mmol) in dioxane (3 mL) is placed in an ultrasonic bath for 45 minutes. 4-Piperidin-4-yl-butyric acid methyl ester hydrochloride (415 mg; 2.0 mmol, prepared in accordance with Example 131) and 1-bromo-4-tert-butyl-benzene (426 mg; 2.00 mmol) are then added and the reaction mixture is stirred for 2 hours under reflux. New catalyst solution (prepared as above from palladium (II) acetate (63 mg; 0.28 mmol), (±)-2,2′-bis-diphenylphosphanyl-[1,1′]binaphthalenyl (258 mg; 0.41 mmol), cesium carbonate (1.30 g; 4.00 mmol) and dioxane (3 mL) is prepared with the aid of an ultrasonic bath and added to the reaction mixture. After stirring under reflux for 3 hours, the mixture is diluted with ethyl acetate and is filtered. The filtrate is concentrated under high vacuum and the obtained residue is purified by column chromatography on silica gel (hexanes/dichloromethane 50:50 v/v to 100) to afford the desired compound (385 mg; 1.21 mmol).

Workup

  1. temperatureunder reflux
  2. customis prepared with the aid of an ultrasonic bath
  3. additionadded to the reaction mixture
  4. stirringAfter stirring
  5. temperatureunder reflux for 3 hours
  6. filtrationis filtered
  7. concentrationThe filtrate is concentrated under high vacuum
  8. customthe obtained residue is purified by column chromatography on silica gel (hexanes/dichloromethane 50:50 v/v to 100)

Sources & evidence

ORD record
ord-b01eed22ad0245cfb78bda14fee82a07
Source dataset
uspto-grants-2015_08
Patent number
US09096524B2

Reaction notes

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