Cesium carbonate → 3-[1-(4-Tert-butyl-phenyl)-piperidin-4-yl]-propionic acid methyl ester

HRID 511183Notes

Reaction equation

HRID 511183 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:65])[CH2:57][CH2:58][CH:59]1[CH2:64][CH2:63][NH:62][CH2:61][CH2:60]1.Br[C:67]1[CH:72]=[CH:71][C:70]([C:73]([CH3:76])([CH3:75])[CH3:74])=[CH:69][CH:68]=1>O1CCOCC1.C(OCC)(=O)C.C([O-])(=O)C.[Pd+2].C([O-])(=O)C>[CH3:54][O:55][C:56](=[O:65])[CH2:57][CH2:58][CH:59]1[CH2:64][CH2:63][N:62]([C:67]2[CH:72]=[CH:71][C:70]([C:73]([CH3:76])([CH3:75])[CH3:74])=[CH:69][CH:68]=2)[CH2:61][CH2:60]1

Participants

8

Reactant 4

HCID 10796Cesium carbonateHCID 775951-Bromo-4-tert-butylbenzeneHCID 634876Binap, (A+-)-HCID 49761244Methyl 3-(piperidin-4-yl)propanoate hydrochloride

Product 1

HCID 585763793-[1-(4-Tert-butyl-phenyl)-piperidin-4-yl]-propionic acid methyl esterYield 48.5%

Reagents, catalysts & solvents 3

HCID 167845palladium(II) acetateCatalystHCID 8857Ethyl AcetateSolventHCID 312751,4-DioxaneSolvent

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 25 minutes. 3-Piperidin-4-yl-propionic acid methyl ester hydrochloride (415 mg, 2.0 mmol, prepared in accordance with Example 138) and 1-bromo-4-tert-butyl-benzene (426 mg; 2.00 mmol) are then added and the reaction mixture is stirred for 7 hours under reflux. The mixture is then diluted with ethyl acetate, filtered and the filtrate is concentrated under high vacuum. The obtained residue is purified by column chromatography on silica gel (hexanes/dichloromethane 50:50 v/v to 100) to afford the desired compound (295 mg; 0.97 mmol).

Workup

  1. temperatureunder reflux
  2. filtrationfiltered
  3. concentrationthe filtrate is concentrated under high vacuum
  4. customThe obtained residue is purified by column chromatography on silica gel (hexanes/dichloromethane 50:50 v/v to 100)

Sources & evidence

ORD record
ord-eb901d46a69244869f7f204eab1d7173
Source dataset
uspto-grants-2015_08
Patent number
US09096524B2

Reaction notes

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