1-[3-(p-fluorobenzoyl)propyl]-4-hydroxy-4-(p-tolyl)piperidinium chloride
![1-[3-(p-fluorobenzoyl)propyl]-4-hydroxy-4-(p-tolyl)piperidinium chloride Structure](CAS/GIF/3871-82-7.gif)
- CAS No.
- 3871-82-7
- Chemical Name:
- 1-[3-(p-fluorobenzoyl)propyl]-4-hydroxy-4-(p-tolyl)piperidinium chloride
- Synonyms
- Meldol;Luvatrene;Methylperidol HCl;Moperone hydochloride;4'-Fluoro-4-(4-hydroxy-4-p-tolylpiperidino)butyrophenone, hydrochloride;1-[3-(p-fluorobenzoyl)propyl]-4-hydroxy-4-(p-tolyl)piperidinium chloride;Butyrophenone, 4'-fluoro-4-(4-hydroxy-4-p-tolylpiperidino)-, hydrochloride;1-Butanone, 1-(4-fluorophenyl)-4-[4-hydroxy-4-(4-methylphenyl)-1-piperidinyl]-, hydrochloride
- CBNumber:
- CB5922970
- Molecular Formula:
- C22H27ClFNO2
- Molecular Weight:
- 391.9066832
- MDL Number:
- MFCD01737621
- MOL File:
- 3871-82-7.mol
| Melting point | 216-218° |
|---|---|
| EWG's Food Scores | 1 |
| FDA UNII | 2Z2633815T |
1-[3-(p-fluorobenzoyl)propyl]-4-hydroxy-4-(p-tolyl)piperidinium chloride Chemical Properties,Uses,Production
Originator
Luvatren,Cilag
Manufacturing Process
A solution of 95 parts of methyl bromide in 356 parts of ether was added
portionwise to a refluxing suspension of 24 parts of magnesium in 214 parts
of ether. The mixture was refluxed for 2 hours, and 92 parts of 4-
methylacetophenone were added in the course of 90 minutes. The refluxing
was continued for 3 hours, and the mixture was stirred for 24 hours at room
temperature. The Grignard complex was destroyed by the addition of
ammonium chloride and 10% hydrochloric acid. The mixture was extracted
with ether and the ether extracts were washed with 10% sulfuric acid and
then with water. Then extracts were dried over anhydrous calcium chloride,
filtered, and concentrated in vacuum to remove the solvent. About 0.5 part of
hydroquinone was added to the residue, which was then heated to a
temperature of 100-110°C at 50 mm. The distillate was extracted with ether
and the ether extracts were dried over anhydrous calcium chloride and
filtered. A small quantity of hydroquinone was added to the ether. The solution
was fractionated by distillation to yield 4-methyl-α-methylstyrene boiling at
about 72-74°C at 80 mm.
A mixture of 856 parts of ammonium chloride and 3000 parts of 36%
formaldehyde was stirred and heated to about 60°C. With cooling to maintain
this temperature, 944 parts of 4-methyl-α-methylstyrene were added slowly.
After the addition was completed, the mixture was stirred at room
temperature until the temperature of the reaction mixture dropped to about
40°C. After 2000 parts of methanol were added, the stirring was continued for
20 hours. The methanol was removed in vacuum and the residue was diluted
with 3000 parts of concentrated hydrochloric acid. For 4 hours, the mixture
was heated with stirring at a temperature of 100°C. The mixture was cooled,
diluted with 2000 parts of water, and made alkaline with 15 N sodium
hydroxide solution. The reaction mixture was extracted with benzene, and the
benzene extracts were dried over anhydrous potassium carbonate and filtered.
The benzene was removed from the filtrate. The remaining residue was
distilled in vacuum to yield 4-(p-tolyl)-1,2,3,6-tetrahydropyridine. This base
was dissolved in benzene. Dry, gaseous hydrogen chloride was passed through
the solution, whereupon there precipitated the hydrochloride, which was
collected on a filter. The 4-(p-tolyl)-1,2,3,6-tetrahydropyridine hydrochloride
boiling at about 162-170°C/10 mm Hg.
While the temperature was being maintained at about 10-20°C, anhydrous
hydrogen bromide gas was passed for 7 hours through a solution of 160 parts
of 4-(p-tolyl)-1,2,3,6-tetrahydropyridine in 500 parts of acetic acid. The
mixture was stirred during the addition of the hydrogen bromide gas. The
mixture was then allowed to stand at room temperature of 16 hours. The
acetic acid and the excess hydrogen bromide were removed in vacuum at a
bath temperature of less than 40°C. The residue was treated with ether. This
solution was cooled, and the product was collected on a filter to give the 4-(ptolyl)-4-bromopiperidine hydrobromide. A solution of 160 parts of above
prepared hydrobromide in 3000 parts of water was treated with 100 parts of
20% sodium hydroxide solution. The resulting precipitate was recovered by
filtration and washed with water. The precipitate was then dissolved in
toluene, and the solution was dried over anhydrous potassium carbonate and
filtered. The filtrate was cooled to 0°C. The crystalline product thus obtained
was collected on a filter to yield 4-(p-tolyl)-piperidin-4-ol; MP: 136-137°C.
To a suspension of 341 parts of aluminium chloride in 1740 parts of carbon
disulphide were added 96 parts of fluorobenzene with stirring and cooling.
While the temperature was maintained at about 10°C, 141 parts of γ-
chlorobutyryl chloride were added. After the addition was completed, the
cooling bath was removed and the stirring was continued for 2 hours. The
reaction mixture was poured into ice water. The organic layer was separated,
washed with water, dried over anhydrous sodium sulfate, and filtered. The
filtrate was concentrated under reduced pressure and the residue was distilled
to yield γ-chloro-p-fluorobutyrophenone. BP: at about 136-142°C/6 mm Hg.
3.7 parts by weight of it, 14.16 parts of 4-(p-tolyl)-piperidin-4-ol, 0.1 parts KI
and 150 parts by volume of toluene was treated in the pressure vessel at
140-150°C for 72 hours. On cooling to room temperature the reaction mixture
was filtered. The solid residue was treated with mixture of water and ether
and ethereal layer added to filtrate from original with water and pressed as
dry as possible on the filter. It was then dissolved in 1500 parts by volume of
boiling toluene to which anhydrous potassium carbonate was added to remove
the remaining water. The mixture was filtered and the filtrate cooled to 0°C.
The was p-fluoro-4-(4-hydroxy-4-p-tolyl-piperidino)butyrophenone. MP of
chlorohydrate: 216-218°C.
Therapeutic Function
Neuroleptic
1-[3-(p-fluorobenzoyl)propyl]-4-hydroxy-4-(p-tolyl)piperidinium chloride Preparation Products And Raw materials
1-[3-(p-fluorobenzoyl)propyl]-4-hydroxy-4-(p-tolyl)piperidinium chloride Suppliers
| Supplier | Tel | Country | ProdList | Advantage | |
|---|---|---|---|---|---|
| TargetMol Chemicals Inc. | +1-781-999-5354 +1-00000000000 | marketing@targetmol.com | United States | 19892 | 58 |
| Hangzhou MolCore BioPharmatech Co.,Ltd. | +86-057181025280; +8617767106207 | sales@molcore.com | China | 49739 | 58 |
| TargetMol Chemicals Inc. | 4008200310 | marketing@tsbiochem.com | China | 24017 | 58 |
| Supplier | Advantage |
|---|---|
| TargetMol Chemicals Inc. | 58 |
| Hangzhou MolCore BioPharmatech Co.,Ltd. | 58 |
| TargetMol Chemicals Inc. | 58 |