Aceclidine CAS 827-61-2
Introduction：Basic information about Aceclidine CAS 827-61-2, including its chemical name, molecular formula, synonyms, physicochemical properties, and safety information, etc.
Aceclidine Basic information
| Product Name: | Aceclidine |
| Synonyms: | 1-AZABICYCLO[2.2.2]OCTAN-3-OL, ACETATE (ESTER);3-Acetoxyquinuclidine;Acetic acid 1-azabicyclo[2.2.2]octane-3-yl ester;Acetic acid quinuclidin-3-yl ester;Quinuclidine-3-ol acetate;quinuclidin-3-yl acetate;1-azabicyclo[2.2.2]octan-3-yl acetate;3-Quinuclidinol acetate ester |
| CAS: | 827-61-2 |
| MF: | C9H15NO2 |
| MW: | 169.22 |
| EINECS: | 212-574-1 |
| Product Categories: | |
| Mol File: | 827-61-2.mol |
Aceclidine Chemical Properties
| Boiling point | 298.52°C (rough estimate) |
| density | 1.0873 (rough estimate) |
| refractive index | 1.4780 (estimate) |
| storage temp. | Sealed in dry,Store in freezer, under -20°C |
| form | <34°C Solid,>36°C Liquid |
| pka | 9.22±0.33(Predicted) |
| color | Off-white to light yellow |
| InChI | InChI=1S/C9H15NO2/c1-7(11)12-9-6-10-4-2-8(9)3-5-10/h8-9H,2-6H2,1H3 |
| InChIKey | WRJPSSPFHGNBMG-UHFFFAOYSA-N |
| SMILES | N12CCC(CC1)C(OC(=O)C)C2 |
Safety Information
| Toxicity | LD50 scu-rat: 225 mg/kg ARZNAD 18,320,68 |
| Originator | Glacostat ,MSD-Chibret ,France ,1966 |
| Uses | analgesic (topical), depletes Substance P, neurotoxic |
| Definition | ChEBI: Acetic acid 1-azabicyclo[2.2.2]octan-3-yl ester is a member of quinuclidines. |
| Manufacturing Process | A mixture of 274 g of methyl isonicotinate, 367 g of ethyl bromoacetate and125 cc of ethyl alcohol was stirred without heating for 4 hours in a flaskequipped with a reflux condenser. (The reaction was exothermic andprecautions were taken to keep the temperature below 70°C.) The reactionmixture was then left for 15 hours at room temperature. The reaction product (1-carbethoxymethyl-4-carbornethoxy-pyridiniumbromide) was obtained in crystalline form. (It formed prisms melting at 166-169°C after recrystallization from a mixture of isopropanol and acetone.) Itwas not necessary to isolate it. For the following reduction step, the reactionmixture was brought into solution by the addition of about 1 liter of warmethyl alcohol. It was then hydrogenated at about 30 atm pressure in thepresence of 2 g of platinum oxide. The temperature rose during this reactionto about 40°C. After the calculated amount of hydrogen had been absorbed,the catalyst was filtered off, the solution was concentrated in vacuum, and theresidual syrup was dissolved in ice water. Benzene was added and the mixturewas made alkaline with an excess of concentrated ice cold potassiumcarbonate solution. The temperature was kept low by continuous addition ofice, and the benzene layer was separated and dried with sodium sulfate. Thedried benzene solution was concentrated in vacuum and the residual oil wasdistilled in vacuum. BP 30 mm = 175-182°C, nD25= 1.4613-1.4628. Duringthe reduction, partial alcoholysis occurred, and the product isolated was 1-carbethoxymethyl-4-"carbalkoxy"-piperidine, wherein "carbalkoxy" representsa mixture of carbomethoxy and carbethoxy. 100 g of potassium were pulverized in 200 cc of hot toluene in a heatedthree-neck flask equipped with an efficient condenser, stirrer and droppingfunnel. To the refluxing potassium suspension were added in small portions229 g of the product of the previous step and about 700 cc of toluene. Thisaddition had to be carried out very cautiously; the onset of the exothermicreaction is sometimes delayed. The addition was finished in about 1 hour. Tocomplete the reaction, the refluxing and stirring were continued for about 4hours. The reaction mixture was then cooled to about +5°C and about 50 ccisopropanol were added to decompose unreacted potassium. Then 2.5 liters ofconcentrated hydrochloric acid were added and the mixture was refluxed for15 hours, and then concentrated in vacuum to dryness. To the residue wasadded with cooling an excess of 50% potassium hydroxide. Ether was thenadded and the resulting mixture was filtered through a fritted glass funnel,thus removing the precipitated potassium chloride. The ethereal and aqueouslayers were separated, and the aqueous layer was extracted repeatedly with500 cc portions of ether. The organic solutions were combined, dried over sodium sulfate and concentrated in vacuum. Aqueous hydrochloric acid wasadded to the residue until the solution became acid. The mixture was thendiluted with distilled water to about 300 cc, heated with decolorizing charcoal,filtered and concentrated in vacuum to dryness. The residue was treated withisopropanol, and the precipitated crystalline product was filtered off. Theproduct was recrystallized from a mixture of water and isopropanol and wasidentified as 1-azabicyclo[2.2.2]-3-octanone hydrochloride; prisms, MP 311-313°C, with decomposition. A solution of 50 g of the above ketone-hydrochloride in 30 cc of water wasmade alkaline by the addition of 30 g of potassium hydroxide. After the alkaliwas dissolved, 35 g of granular potassium carbonate were added. The freebasic ketone was then extracted from the viscous mixture by shaking with 4portions of hot benzene (300 cc in each portion). The benzene extracts weredecanted, filtered over sodium sulfate in order to remove any suspendedalkali, and concentrated in vacuum. The residual lszabicyclo[2.2.2]-3-octanonewas purified by sublimation (50-70°C/0.5 mm Hg); it can also be purified byrecrystallization from petroleum ether. It formed feathery crystals melting at147-148°C. The product was reduced as follows:A solution of 50 g of 1-azabicyclo[2.2.2]-3-octanone hydrochloride in 200 ccof water was hydrogenated at room temperature and 50 atm pressure with 1g of platinum oxide as catalyst. After the calculated amount of hydrogen hadbeen absorbed, the mixture was filtered and concentrated in vacuum todryness. The residual product was recrystallized from a mixture of methanoland acetone and formed prisms melting above 300°C. It was identified as 1-azabicyclo[2.2.2]-3-octanol hydrochloride. A solution of 50 g of 1-azabicyclo[2.2.2]-3-octanol hydrochloride in 30 ccwater was made alkaline with 30 g of potassium hydroxide. After the alkaliwas dissolved 35 g of granular potassium carbonate were added. The freebasic alcohol was then extracted from the viscous mixture by shaking withfour portions of boiling benzene (300 cc in each portion). The benzeneextracts were decanted and filtered over anhydrous sodium sulfate, to removeany suspended alkali. The combined benzene solutions were concentrated invacuum. The residue was recrystallized from benzene and identified aslszabicyclo[2.2.2]-3-octanol, MP 221-223°C. The product can also be purifiedby recrystallization from acetone, or by sublimation in vacuum (120°C/20 mmHg). The alcohol was reacted with acetic anhydride to give the productaceclidine. |
| Brand name | Cholinergic Glaucostat (Kingshill Pharmaceuticals,Inc, Switzerland). |
| Therapeutic Function | Miotic, Cholinomimetic |
| Safety Profile | Poison by ingestion, subcutaneous,and intravenous routes. When heated to decomposition itemits toxic fumes of NOx. |
| References | [1] Patent: US5387409, 1995, A |
Aceclidine Preparation Products And Raw materials
| Raw materials | Potassium-->Hydrogen-->Ethyl bromoacetate-->Methyl isonicotinate-->Potassium hydrogen phthalate-->3-Quinuclidinol-->Water-->Acetic anhydride-->Pyridine |
