ChemicalBook CAS DataBase List 4-PIPERIDIN-4-YL-BENZOIC ACID

4-PIPERIDIN-4-YL-BENZOIC ACID synthesis

5synthesis methods

Product Name:4-PIPERIDIN-4-YL-BENZOIC ACID
CAS Number:196204-01-0
Molecular formula:C12H15NO2
Molecular Weight:205.25

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Yield: 63%

Reaction Conditions:

Stage #1:oxalyl dichloride;1-(4-Phenyl-piperidin-1-yl)-ethanone;aluminum (III) chloride in dichloromethane at -78 - 20;Friedel Crafts Acylation;
Stage #2: with hydrogenchloride;sodium hydroxide in water; pH=5 at 0;
Stage #3: with hydrogenchloride in water for 18 h;Heating / reflux;

Steps:

8.9
4-Phenylpiperidine (10.0 g, 62 mmol) and pyridine (5.74 mL, 71 mmol) were dissolved in DCM (80 mL) and cooled to 0 "C. A solution of acetyl chloride (4.00 mL, 71 mmol) in DCM (20 mL) was added drop wise to the above solution. The mixture was then stirred for 2 h at RT and when deemed to be complete by hplc, extracted with water, dried and concentrated in vacuo to afford a light yellow oil (10.6 g, 84%) which solidified on standing and was used without further purification. The yellow oil (10.6 g, 52.2 mmol) was dissolved in DCM and cooled to - 78 "C and treated with oxalyl chloride (18.3 mL, 209 mmol) drop wise followed by the addition of aluminium chloride (20.9 g, 157 mmol) in portions. When the addition was complete, the flask was placed in an ice-salt bath, and the mixture stirred at - 20 "C for 3h and then at RT overnight. The mixture was then poured onto ice-water and extracted with DCM (100 mL x 3), dried and concentrated in vacuo. The residue was dissolved in aq. NaOH (2N) and HCI (6N) was added at 0 "C to acidify the solution to pH 5. The precipitate (7.9 g) was filtered off and washed with water (200 mL). The residue was then suspended in 6N HCI and heated at reflux for EPO 18h. The solvent was evaporated and the residue was recrystallised from ethanol. Crystals were filtered off and provided the title compound (5.05 g, 63%).

References:

MEDIVIR AB WO2007/6714, 2007, A1 Location in patent:Page/Page column 85-86