Day: September 11, 2020

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

Preparation of 3-fluorobenzyl quinuclidine-4-carboxylate (compound 91)A mixture of quinuclidine-4-carboxylic acid hydrochloride (100 mg, 0.52 mmol) and thionyl chloride (500 mu, 6.85 mmol) was refluxed for 2 hours. The reaction was cooled at room temperature and the solvent was accurately removed. The residue was suspended in dry DCM and treated with (3-fluorophenyl)methanol (65.8 mg, 0.52 mmol). The reaction was stirred at room temperature for 24 hours. The solvent was evaporated, the residue was dissolved in water (1 ml), basified with NaHCO3 and extracted twice with EtOAc. The combined organic layers were dried over Na2SO4, filtered and evaporated to obtain 3-fluorobenzyl quinuclidine-4-carboxylate (41 mg, 29.8 % yield), which was used in the next step without any further purification.

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; CHIESI FARMACEUTICI S.p.A.; AMARI, Gabriele; RICCABONI, Mauro; DE ZANI, Daniele; WO2012/146515; (2012); 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

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., 40117-63-3

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.

A solution of phenyllithium (1 .9 M in 70 cyclohexane/30 ether, 22.30 mL, 42.40 mmol) was cooled down to -30C under nitrogen. A solution of ethyl 1 -azabicyclo[2.2.2]octane-4-carboxylate (III, 2.0 g, 10.90 mmol) in THF (27.0 mL) was slowly added to the reaction mixture at -30C over 25 mins. The reaction mixture was allowed to warm up to room temperature over 16h. The reaction was quenched with water (10.0 mL) and then evaporated to dryness under vacuum. Water (40.0 mL) and ethyl acetate (40.0 mL) were added, causing a white solid to crash out. This solid was filtered off under vacuum, to give a white powder (2.46 g, 76.8%). 1 -azabicyclo[2.2.2]oct-4-yl(diphenyl)methanol (IV): ^H-NMR (300 MHz, CDC ) delta 7.54 – 7.51 (m, 3H), 7.33 – 7.20 (m, 6H), 2.85 – 2.80 (m, 6H), 1 .78 – 1.72 (m, 6H). MS (ESI) m/z calcd for C20H23NO: 293, found 294 [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,22766-68-3,Ethyl quinuclidine-4-carboxylate,its application will become more common.

Reference£º
Patent; HOVIONE SCIENTIA LIMITED; TURNER, Craig; LOURENCO, Nuno Torres; SOBRAL, Luis; ANTUNES, Rafael; SANTOS, Maria; ESPADINHA, Margarida; (35 pag.)WO2018/87561; (2018); 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

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,22766-68-3,Ethyl quinuclidine-4-carboxylate,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

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

Preparation of 3-fluorobenzyl quinuclidine-4-carboxylate (compound 91)A mixture of quinuclidine-4-carboxylic acid hydrochloride (100 mg, 0.52 mmol) and thionyl chloride (500 mu, 6.85 mmol) was refluxed for 2 hours. The reaction was cooled at room temperature and the solvent was accurately removed. The residue was suspended in dry DCM and treated with (3-fluorophenyl)methanol (65.8 mg, 0.52 mmol). The reaction was stirred at room temperature for 24 hours. The solvent was evaporated, the residue was dissolved in water (1 ml), basified with NaHCO3 and extracted twice with EtOAc. The combined organic layers were dried over Na2SO4, filtered and evaporated to obtain 3-fluorobenzyl quinuclidine-4-carboxylate (41 mg, 29.8 % yield), which was used in the next step without any further purification.

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; CHIESI FARMACEUTICI S.p.A.; AMARI, Gabriele; RICCABONI, Mauro; DE ZANI, Daniele; WO2012/146515; (2012); 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 8: (S)-4- ((1- (5- (2-methoxyquinolin-1-ium-3-yl)oxazol-2-yl)- 7- (methylamino)- 7-oxoheptyl)carbamoyl)quinuclidin-1-ium mono L-tartrate salt (F8)A solution of 4-carboxyquinuclidin-1-ium chlorhydrate (1.3 eq.) in DMF (0.1 M) was treated with HOBt (1.3 eq.), EDC HC1 (1.3 eq.) and DIPEA (1.3 eq.). The reaction mixture was stirred at room temperature for 10 minutes and then added to F7. The reaction was stirred for at RT for 48 h, filtered and directly purified by RP-HPLC (Acetonitrile/H20 + 0.1 % TFA). The product was obtained as TFA salt which was partitioned between DCM and sat. aq. NaHCO3. Theorganic phase was separated dried over Na2504 and concentrated under reduced pressure. The resulting 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. MS (ESj C29H37N504: 520 (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,40117-63-3,Quinuclidine-4-carboxylic acid hydrochloride,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, 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

Preparation of 3-fluorobenzyl quinuclidine-4-carboxylate (compound 91)A mixture of quinuclidine-4-carboxylic acid hydrochloride (100 mg, 0.52 mmol) and thionyl chloride (500 mu, 6.85 mmol) was refluxed for 2 hours. The reaction was cooled at room temperature and the solvent was accurately removed. The residue was suspended in dry DCM and treated with (3-fluorophenyl)methanol (65.8 mg, 0.52 mmol). The reaction was stirred at room temperature for 24 hours. The solvent was evaporated, the residue was dissolved in water (1 ml), basified with NaHCO3 and extracted twice with EtOAc. The combined organic layers were dried over Na2SO4, filtered and evaporated to obtain 3-fluorobenzyl quinuclidine-4-carboxylate (41 mg, 29.8 % yield), which was used in the next step without any further purification.

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; CHIESI FARMACEUTICI S.p.A.; AMARI, Gabriele; RICCABONI, Mauro; DE ZANI, Daniele; WO2012/146515; (2012); 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, 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-(2-methoxyquinolin-1-ium-3-yl)-JH-imidazol-2-yl)- 7-(methylamino)- 7-oxoheptyl)carbamoyl)quinuclidin-1-ium mono L-tartrate salt (A5) 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 minutes and then added to a solution of A4 in DMF (0.2 M). The reaction was stirred at RT for 2 h and subsequently was purified by RP-HPLC (Acetonitrile/H20 + 0.1 % TFA). Theproduct was obtained as TFA salt which was partitioned between DCM and sat. aq. NaHCO3. The organic phase was separated, dried over Na2504 and concentrated under reduced pressure. The resulting syrup was dissolved in acetonitrile/H20 (2:3) and treated with L-tartaric acid (1 eq.). The resulting solution was lyophilized to obtain the title compound. 1H-NMR (400 MHz, 300 K, DMSO-d6) oe 8.73 (br s, 1H), 7.94 (t, 2H, J 9.6 Hz), 7.76 (d, 1H, J 8.0 Hz), 7.67 (br s,1H), 7.60 (m, 2H), 7.42 (t, 1H, J8.0 Hz), 5.02 (m, 1H), 4.13 (s, 3H), 3.93 (s, 2H), 3.18 (t, 6H, J7.2 Hz), 2.54 (d, 3H, J4.4 Hz), 2.05-1.91 (m, 8H), 1.51-1.23 (m, 8H). MS (ESj C29H38N603:519 (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,40117-63-3,Quinuclidine-4-carboxylic acid hydrochloride,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

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.

(Quinuclidin-4-yl)carboxylic acid was prepared from 4-cyanoquinuclidine (Oakwood Products) following the procedure of Grob and Renk, Helv. Chim. Acta, 37, 1681 (1954). To a stirred suspension of quinuclidine-4-carboxylic acid hydrochloride (100 mg, 0.523 mmol) in 3 mL of anhydrous tetrahydrofuran at 0 C. was added borane methylsulfide complex (42 mg, 0.553 mmol). The mixture was stirred at room temperature for 1 hr and heated to reflux overnight. The reaction was cooled to 0 C. and carefully treated with 1 mL of methanol. The solvent was then removed under reduced pressure to leave the desired alcohol. Yield 36 mg. MS (m/e): 141.

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