Day: September 3, 2020

A common heterocyclic compound, 22766-68-3,Ethyl quinuclidine-4-carboxylate, its traditional synthetic route has been very mature, but the traditional synthetic route has various shortcomings, such as complicated route, low yield, poor purity, etc., below Introduce a new synthetic route. 22766-68-3

Example 32 Preparation of 1-butyl-4-[hydroxy(di-3-thienyl)methyl]-1-azoniabicyclo[2.2.2]octane bromide A solution of n-Butyl lithium (2.5M in hexanes, 5.0 mL, 12.5 mmol) was chilled to -78 C. under Ar. 3-Bromothiophene (1.15 mL, 12.3 mmol) dissolved in ethyl ether (4.0 mL) was slowly added to the reaction mixture. The reaction was stirred for 30 min and then ethyl 1-azabicyclo[2.2.2]octane-4-carboxylate (0.7640 g, 4.16 mmol) in THF/Et2O (4 mL/4 mL) was added. The reaction was allowed to warm up from -78 C. to room temperature over 16 h then slowly quenched with water. The reaction was concentrated and the resulting brown solid was taken up in water and DCM. The organic phase was separated, dried over MgSO4, filtered and concentrated under vacuum to give a brown solid. The solid was dissolved in DMSO and purified by preparatory HPLC to give the title compound (0.1736 g, 9.4%). EI-MS m/z 362(M+) Rt (1.73 min)., 22766-68-3

This compound has a wide range of applications. It is believed that with the continuous development of the source of the synthetic route,22766-68-3,Ethyl quinuclidine-4-carboxylate,its application will become more common.

Reference£º
Patent; Laine, Damane I.; Palovich, Michael R.; McCleland, Brent W.; Neipp, Christopher E.; Thomas, Sonia M.; US2007/185155; (2007); A1;,
Quinuclidine – Wikipedia
Quinuclidine | C7H13N | ChemSpider

A common heterocyclic compound, 40117-63-3,Quinuclidine-4-carboxylic acid hydrochloride, its traditional synthetic route has been very mature, but the traditional synthetic route has various shortcomings, such as complicated route, low yield, poor purity, etc., below Introduce a new synthetic route. 40117-63-3

Step 4. Quinuclidin-4-ylcarbonyl chloride hydrochloride Quinuclidine-4-carboxylic acid hydrochloride (0.192 g, 0.001 mole) was suspended in dichloromethane (5 ml) and dimethylformamide (1 drop) and oxalyl chloride (0.436 ml. 0.635 g, 0.005 mole) were added. The resulting suspension was heated to reflux under an atmosphere of argon for six hours. Following concentration of the suspension in vacuo the residue was suspended in dichloromethane, concentrated in vacuo and finally dried in vacuo to give the title compound as a pale brown solid.

This compound has a wide range of applications. It is believed that with the continuous development of the source of the synthetic route,40117-63-3,Quinuclidine-4-carboxylic acid hydrochloride,its application will become more common.

Reference£º
Patent; SmithKline Beecham p.l.c.; US6281226; (2001); B1;,
Quinuclidine – Wikipedia
Quinuclidine | C7H13N | ChemSpider

A common heterocyclic compound, 40117-63-3,Quinuclidine-4-carboxylic acid hydrochloride, its traditional synthetic route has been very mature, but the traditional synthetic route has various shortcomings, such as complicated route, low yield, poor purity, etc., below Introduce a new synthetic route. 40117-63-3

Step 5: (S)-4-((1-(5-(6-methoxynaphthalen-2-yl)-JH-imidazol-3-ium-2-yl)- 7-(methylamino)- 7-oxoheptyl)carbamoyl)quinuclidin-1-ium mono L-tartrate salt (E5) A solution of 4-carboxyquinuclidin-1-ium chlorhydrate (1.3 eq.) in DMF (0.2 M) was treated with TBTU (1.3 eq.) and NMM (2.6 eq.). The reaction mixture was stirred at room temperature for 10 mm and then added to a solution of E4 in DMF (0.2 M). The reaction was stirred at RT for 2 h, then filtered and purified by RP-HPLC (CH3CN/H20 + 0.1 % TFA). The product was obtained as TFA salt which was partitioned between EtOAc and sat. aq. NaHCO3. The organicphase was separated, dried (Na2504) and concentrated under reduced pressure. The resulting pale yellow solid was dissolved in acetonitrile/H20 (1:1) and treated with L-tartaric acid (1 eq.). The resulting solution was lyophilized to obtain the title compound. (400 MHz, 300K, DMSOd 6) oe: 11.5 (br s, 1H), 8.14 (br s, 1H), 7.95-7.73 (m, 4H), 7.66 (m, 1H), 7.54 (m, 1H), 7.27 (d, 1H, J2 Hz), 7.12 (dd, 1H, J8.8 and 2.4 Hz), 4.99 (m, 1H), 3.89 (s, 2H), 3.86 (s, 3H), 3.16 (m,6H), 2.54 (d, J4.4 Hz), 3H), 2.02 (t, 2H, J7.4 Hz), 2.01 (m, 6H), 1.83 (m, 2H), 1.48 (m, 2H),1.35-1.15 (m, 4H). MS (ESj C30H39N503: 518 (M+H).

This compound has a wide range of applications. It is believed that with the continuous development of the source of the synthetic route,Quinuclidine-4-carboxylic acid hydrochloride,40117-63-3,its application will become more common.

Reference£º
Patent; IRBM SCIENCE PARK S.P.A.; C.N.C.C.S. SCARL COLLEZIONE NAZIONALE DEI COMPOSTI CHIMICI E CENTRO SCREENING; ALTAMURA, Sergio; BIANCOFIORE, Ilaria; BRESCIANI, Alberto; FERRIGNO, Federica; HARPER, Steven; LAUFER, Ralph; ONTORIA ONTORIA, Jesus Maria; MALANCONA, Savina; MONTEAGUDO, Edith; NIZI, Emanuela; ORSALE, Maria Vittoria; PONZI, Simona; PAONESSA, Giacomo; SUMMA, Vincenzo; VENEZIANO, Maria; WO2014/67985; (2014); A1;,
Quinuclidine – Wikipedia
Quinuclidine | C7H13N | ChemSpider

A common heterocyclic compound, 22766-68-3,Ethyl quinuclidine-4-carboxylate, its traditional synthetic route has been very mature, but the traditional synthetic route has various shortcomings, such as complicated route, low yield, poor purity, etc., below Introduce a new synthetic route. 22766-68-3

Example 13: Preparation of 4-[cyano(di-2-thienyl)methyl]-1-[3- (DhenVIoxVlDroDVIl-1-azoniabicvclo [2.2.210ctane bromide;. 1-Azabicyclof2. 2. 2 Joct-4-yl(di-2-thienyl)methanol; A solution of 2-thienyllithium (1.0 M in THF, 13.0 mL, 13 mmol) was chilled down to -30 C under Ar. Ethyl 1-azabicyclo[2.2.2]octane-4-carboxylate (0.77 g, 4.20 mmol) in THF (12 mL) was slowly added to the 2-thienyllithium at-30 C over 40 min. The reaction was allowed to warm up to room temperature for overnight. The reaction was quenched with H20 and then diluted with EtOAC, hexane and DCM causing a solid to crash out of solution. The solid was filtered off, resulting in the desired compound (0.9132 g, 71.3%). EI-MS m/z 306 (M+) Rt (1.33 min).

This compound has a wide range of applications. It is believed that with the continuous development of the source of the synthetic route,22766-68-3,Ethyl quinuclidine-4-carboxylate,its application will become more common.

Reference£º
Patent; GLAXO GROUP LIMITED; WO2005/112644; (2005); A2;,
Quinuclidine – Wikipedia
Quinuclidine | C7H13N | ChemSpider

A common heterocyclic compound, 40117-63-3,Quinuclidine-4-carboxylic acid hydrochloride, its traditional synthetic route has been very mature, but the traditional synthetic route has various shortcomings, such as complicated route, low yield, poor purity, etc., below Introduce a new synthetic route. 40117-63-3

To a stirred suspension of quinuclidine-4-carboxylic acid hydrochloride (5.5 g) in 30 mL of dry THF at 0 C. was added borane dimethyl sulfide complex (6.7 g, 3 eq.). The reaction mixture was stirred at room temperature for 1 hr and heated to reflux for 16 hr. It was then quenched with drop-wise addition of methanol (7 mL) at 0 C. The solvent was then removed under reduced pressure, and the crude product obtained was purified by column chromatography (Silica gel, 20% EA:Hexane) to afford the product quinuclidin-4-ylmethanol N-borane complex as a white solid (1.35 g, 30%).

This compound has a wide range of applications. It is believed that with the continuous development of the source of the synthetic route,Quinuclidine-4-carboxylic acid hydrochloride,40117-63-3,its application will become more common.

Reference£º
Patent; CoMentis, Inc.; BILCER, Geoffrey M.; NG, Raymond; (104 pag.)US2016/9706; (2016); A1;,
Quinuclidine – Wikipedia
Quinuclidine | C7H13N | ChemSpider

A common heterocyclic compound, 22766-68-3,Ethyl quinuclidine-4-carboxylate, its traditional synthetic route has been very mature, but the traditional synthetic route has various shortcomings, such as complicated route, low yield, poor purity, etc., below Introduce a new synthetic route. 22766-68-3

1-azabicyclo[2.2.2]oct-4-yl[bis(3-methylphenyl)]methanol A solution of 3-methylphenylmagnesiumbromide (1.0 M in THF, 3.3 mL, 3.3 mmol) was chilled down to 0 C. under Ar. Ethyl 1-azabicyclo[2.2.2]octane-4-carboxylate (0.1484 g, 0.810 mmol) in THF (4 mL) was slowly added to the reaction mixture at 0 C. over 20 min. The reaction was allowed to warm up to room temperature and then heated at 60 C. for 16 h. The reaction was chilled in an ice bath, quenched with saturated NH4Cl, and concentrated under vacuum. The resulting residue was treated with H2O and extracted with EtOAc. The combined organic layers were dried with MgSO4, filtered, and concentrated under vacuum to yield the desired product (0.1806 g, 69.4%). EI-MS m/z 322(M+H+) Rt (1.54 min).

This compound has a wide range of applications. It is believed that with the continuous development of the source of the synthetic route,22766-68-3,Ethyl quinuclidine-4-carboxylate,its application will become more common.

Reference£º
Patent; Laine, Damane I.; Palovich, Michael R.; McCleland, Brent W.; Neipp, Christopher E.; Thomas, Sonia M.; US2007/185155; (2007); A1;,
Quinuclidine – Wikipedia
Quinuclidine | C7H13N | ChemSpider

A common heterocyclic compound, 26458-78-6,Quinuclidine-4-carbonitrile, its traditional synthetic route has been very mature, but the traditional synthetic route has various shortcomings, such as complicated route, low yield, poor purity, etc., below Introduce a new synthetic route. 26458-78-6

Quinuclidine-4-carbonitrile (4 g, 29.4 mmol) was treated with 30 mL of 6 N aqueous HCl solution and stirred under reflux for 16 hr. The reaction mixture was cooled and evaporated to dryness under reduced pressure. The solid obtained was triturated with 20% ether-hexane to afford the HCl salt of quinuclidine-4-carboxylic acid (5.5 g, quantitative).

This compound has a wide range of applications. It is believed that with the continuous development of the source of the synthetic route,26458-78-6,Quinuclidine-4-carbonitrile,its application will become more common.

Reference£º
Patent; CoMentis, Inc.; BILCER, Geoffrey M.; NG, Raymond; (104 pag.)US2016/9706; (2016); A1;,
Quinuclidine – Wikipedia
Quinuclidine | C7H13N | ChemSpider

40117-63-3 A common heterocyclic compound, 40117-63-3,Quinuclidine-4-carboxylic acid hydrochloride, its traditional synthetic route has been very mature, but the traditional synthetic route has various shortcomings, such as complicated route, low yield, poor purity, etc., below Introduce a new synthetic route.

Under the protection of nitrogen, phenyllithium (1.5 – 1.7M cyclohexane/diethyl ether solution (70:30), 30.0 ml, 48.00mmol) solution cooled to -30 C, in -30 C under, 0.5 hours slowly dropping WD2 (2.27g, 12 . 35mmol) of THF (30 ml) solution to the reaction mixture. The reaction liquid heating to room temperature reaction 16 hours, adding water quenching reaction, mixed solution under vacuum to evaporate to dry, adding water and ethyl acetate, to obtain white solid to settle out, filtering to obtain solid, shall WD1 (1.19g). The aqueous phase is further extracted with ethyl acetate, the combined organic layer was dried with anhydrous sodium sulfate, filtered, concentrated under reduced pressure to get the crude product, the crude product of ethyl acetate and hexane processing, filtering to obtain WD1.

This compound has a wide range of applications. It is believed that with the continuous development of the source of the synthetic route,40117-63-3,Quinuclidine-4-carboxylic acid hydrochloride,its application will become more common.

Reference£º
Patent; Sichuan Hai Sike Pharmaceutical Co., Ltd.; Yi Shixu; Fu Li; (6 pag.)CN106810546; (2017); A;,
Quinuclidine – Wikipedia
Quinuclidine | C7H13N | ChemSpider

22766-68-3 A common heterocyclic compound, 22766-68-3,Ethyl quinuclidine-4-carboxylate, its traditional synthetic route has been very mature, but the traditional synthetic route has various shortcomings, such as complicated route, low yield, poor purity, etc., below Introduce a new synthetic route.

Crude preparation: azabicyclo [2.2.2] octane-4-carboxylic acid ethyl ester (18.3g, 0 . 10mol) dissolved in 3L tetrahydrofuran, under the protection of nitrogen, the solution is cooled down 5-15C, dropwise 0.30mol phenyl magnesium bromide. 5-15 C preserving heat and stirring 1 hour later (sampling TLC monitoring reaction progress). Add 10 ml water quenching. The liquid, aqueous phase using 100 ml tetrahydrofuran extraction two, combined with the phase water washing, drying and filtering. Removing part of the solvent under reduced pressure, the rest about 50 ml, residues 20 C stirring sleepovers crystallization. Filtering, washing (petroleum ether 2¡Á20 ml), the filtration cake at 40 C vacuum drying, be yellowish crystal 13.80g, yield 47.1%.Refining wuhu bromine ammonium : crude 100g dissolved in 80 C of 320 ml water-acetone 640 ml mixture, and 5g activated carbon decolourizations, filtering. Filtrate lower the temperature to 25 C, thermal insulation 1 hour. 1-2 hours to lower the temperature to 0-5 C and thermal insulation 3 hours. Filtering, the filter cake is washed with frozen 1:2 acetone-water washing two times (2x20ml). The filtration cake at 60 C vacuum drying, getting white crystalline solid (92g, yield 92%). (Normalization HPLC) purity of 99.25%.

This compound has a wide range of applications. It is believed that with the continuous development of the source of the synthetic route,Ethyl quinuclidine-4-carboxylate,22766-68-3,its application will become more common.

Reference£º
Patent; Anhui Dexinjia Biopharm Co., Ltd.; Li, Xuekun; Xu, Kun; (5 pag.)CN105461710; (2016); A;,
Quinuclidine – Wikipedia
Quinuclidine | C7H13N | ChemSpider