p-Bromochlorobenzene → 3-[1-(4-Chloro-phenyl)-piperidin-4-yl]-propionic acid methyl ester

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-chloro-benzene (383 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 6 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 (345 mg; 1.22 mmol).

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 6 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)

ORD record

ord-3cc85aee19704c1ca8609fd86dd6aee3

Source dataset

uspto-grants-2015_08

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US09096524B2