Day: August 19, 2020

22766-68-3,Ethyl quinuclidine-4-carboxylate,C10H17NO2,SMILES CODES_O=C(C1(CC2)CCN2CC1)OCC,is widely used in the synthesis of drugs.

Ethyl quinuclidine-4-carboxylate (900 mg, 4.91 mmol) was hydrolyzed in a mixture of ethanol (2 mL) and sodium hydroxide (aq) (2M, 7.5 mL) at 50 C. The reaction was followed by TLC (methanol/diethylamine 20/1). After 3 hours the mixture was neutralized with HC1 (2 M) to pH=5 and evaporated. The residue was extracted with methanol which however also extracted NaCl. The extract was evaporated and the solid was extracted with ethanol which was not very effective in extracting the desired zwitterionic amino acid. All extracts and solids were combined and HC1 (2 M) was added to pH< 1 and the mixture was evaporated until it was completely dry. The solid residue was suspended in dichioromethane (10 mL) and oxalyl chloride (25 mmol, 2.3 mL) was added followed by two drops of N,N-dimethylformamide. The mixture was refluxed for 6 hours and then evaporated to dryness. To the residue was added N,N-dimethylformamide (10 mL) and sodium azide (10.4 mmol, 680 mg) and the mixture was stirred at 50 C for 20 h, then partitioned between saturated sodium carbonate and toluene. A three phase liquid system was formed. The toluene phase (on top) was collected, dried, and heated at reflux for 1 hours (visible gas formation occurred before reaching the reflux temperature), then cooled and extracted three times with HC1 (SM, 3 x 20 mL). The aqueous phases were combined and heated at reflux for 1 h, then evaporated to almost dryness and triturated with abs. ethanol. The precipitate was collected and gave the desired 4-aminoquinuclidine as the dihydrochloride (173 mg, 0.87 mmol, 18% yield). ?H NMR (400 MHz, deuterium oxide) 3.68- 3.52 (m, 4H), 2.37-2.23 (m, 4H). 22766-68-3,big data shows that is playing an increasingly important role. Reference£º
Patent; ACADIA PHARMACEUTICALS INC.; BURSTEIN, Ethan, S.; OLSSON, Roger; JANSSON, Karl, Erik; SKOeLD, Niklas, Patrik; WAHLSTROeM, Larisa, Yudina; VON WACHENFELDT, Henrik; BERGNER, Magnus, Gustav Wilhelm; DREISCH, Klaus; POPOV, Kyrylo; KOVALENKO, Oleksnadr; KLINGSTEDT, Per Tomas; (357 pag.)WO2019/40106; (2019); A2;,
Quinuclidine – Wikipedia
Quinuclidine | C7H13N | ChemSpider

22766-68-3,Ethyl quinuclidine-4-carboxylate,C10H17NO2,SMILES CODES_O=C(C1(CC2)CCN2CC1)OCC,is widely used in the synthesis of drugs.

1-azabicyclo[2.2.2]oct-4-yl]bis(4-fluorophenyl)]methanol A solution of 4-fluorophenylmagnesiumbromide (1.0 M in THF, 4.4 mL, 4.4 mmol) was chilled down to 0 C. under Ar. Ethyl 1-azabicyclo[2.2.2]octane-4-carboxylate (0.1973 g, 1.08 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 (0.3152 g, 88.9%). EI-MS m/z 330(M+H+) Rt (1.65 min).

22766-68-3,big data shows that is playing an increasingly important role.

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

22766-68-3,Ethyl quinuclidine-4-carboxylate,C10H17NO2,SMILES CODES_O=C(C1(CC2)CCN2CC1)OCC,is widely used in the synthesis of drugs.

1-Azabicyclo[2.2.2]oct-4-yl(diphenyl)methanol A solution of phenyllithium (1.5-1.7 M in 70 cyclohexane/30 ether, 20.0 mL, 32 mmol) was chilled down to -30 C. under Ar. Ethyl 1-azabicyclo[2.2.2]octane-4-carboxylate (1.51 g, 8.23 mmol) in THF (20 mL) was slowly added to the reaction mixture at -30 C. over 25 min. The reaction was allowed to warm up to room temperature over 16 h. The reaction was quenched with H2O and then evaporated to dryness under vacuum. H2O and EtOAc were added, causing a white solid to crash out. This solid was filtered off, to give the title compound (0.79 g). The aqueous phase was further extracted with EtOAc, the combined organic layers were dried over MgSO4, filtered, and concentrated under vacuum. The crude product was treated with EtOAc and hexane and filtered to yield more of the title compound (0.67 g). Total yield (1.46 g, 60.7%). EI-MS m/z 294(M+H+) Rt (1.37 min).

22766-68-3,big data shows that is playing an increasingly important role.

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

40117-63-3,Quinuclidine-4-carboxylic acid hydrochloride,C8H14ClNO2,SMILES CODES_O=C(C1(CC2)CCN2CC1)O.[H]Cl,is widely used in the synthesis of drugs.

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).

40117-63-3,big data shows that is playing an increasingly important role.

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,Quinuclidine-4-carboxylic acid hydrochloride,C8H14ClNO2,SMILES CODES_O=C(C1(CC2)CCN2CC1)O.[H]Cl,is widely used in the synthesis of drugs.

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).

40117-63-3,big data shows that is playing an increasingly important role.

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

22766-68-3,Ethyl quinuclidine-4-carboxylate,C10H17NO2,SMILES CODES_O=C(C1(CC2)CCN2CC1)OCC,is widely used in the synthesis of drugs.

To a solution of ethyl 1-aza-bicyclo[2.2.2]octane-4-carboxylate (PCT2005104745) (9.610 g, 52.44 mmol) in THF (480 ml) at -780C was added borane-THF complex (73.41 ml,73.41 mmol) and the resulting solution was stirred at this temperature for 3.5 h. The reaction was quenched with slow addition of H2O (50 ml), warmed to RT, and allowed to stir for 45 min. The solution was diluted with EtOAc (100 ml), washed with brine (15 ml), extracted with EtOAc (3 x 50 ml), dried (Na2SO4) and evaporated. The crude product was purified on a CombiFlash companion using 0-50% EtOAc in cyclohexane as eluent to give a bright yellow solid.Yield: 7.236 g (70%)1 H NMR (400 MHz, CDCI3) delta = 4.15 (q, 2H), 3.07 (t, 4H)1 1.96 (t, 4H), 1.26 (t, 3H) ppm.

22766-68-3,big data shows that is playing an increasingly important role.

Reference£º
Patent; ARGENTA DISCOVERY LIMITED; WO2009/60206; (2009); A1;,
Quinuclidine – Wikipedia
Quinuclidine | C7H13N | ChemSpider

22766-68-3,Ethyl quinuclidine-4-carboxylate,C10H17NO2,SMILES CODES_O=C(C1(CC2)CCN2CC1)OCC,is widely used in the synthesis of drugs.

Step 1. A solution of 4-carbethoxyquinuclidine (10.92 g) in THF (155 mL) was treated at-780C with borane-THF (1.0 M, 77.5 mL). The resulting mixture was stirred at -78C for 4 h, then treated with water (50 mL), warmed to room temperature and stirred for an additional hour. The reaction mixture was diluted with ethyl acetate and the aqueous phase was separated and extracted with two further portions of ethyl acetate. The combined organic layers were washed with brine- (twice), dried (MgSO4), filtered and evaporated in vacuo. Purification by silica gel chromatography (eluting with cyclohexane-ethyl acetate [1 :0 to 1 :1]) gave 1-boranyl-1-aza-bicyclo[2.2.2]octane-4- carboxylic acid ethyl ester (7.12 g, 61%) as an off-white solid. 1H NMR (400 MHz, CDCI3) delta 4.16 (2H1 q, J = 6.9), 3.10-3.05 (6H1 m), 1.98-1.93 (6H, m), 1.26 (3H, t, J = 6.9).

22766-68-3,big data shows that is playing an increasingly important role.

Reference£º
Patent; ARGENTA DISCOVERY LIMITED; WO2008/99186; (2008); A1;,
Quinuclidine – Wikipedia
Quinuclidine | C7H13N | ChemSpider

22766-68-3,Ethyl quinuclidine-4-carboxylate,C10H17NO2,SMILES CODES_O=C(C1(CC2)CCN2CC1)OCC,is widely used in the synthesis of drugs.

1 Azabicyclo 2.2.2Joct-4 yl(diphe yl)methanol ;A solution of phenyllithium (1.5-1.7 M in 70 cyclohexane / 30 ether, 20.0 mL, 32 mmol) was chilled down to -30 C under Ar. Ethyl 1-azabicyclo[2.2.2]octane-4- carboxylate (1.51g, 8.23 mmol) in THF (20 mL) was slowly added to the reaction mixture at -30 C over 25 min. The reaction was allowed to warm up to room temperature overnight. The reaction was quenched with H20 and then evaporated to dryness under vacuum. H20 and EtOAc were added, causing a white solid to crash out. This solid was filtered off, to give the title compound (0.79 g). The aqueous phase was further extracted with EtOAc, the combined organic layers were dried over MgS04, filtered, and concentrated under vacuum. The crude product was treated with EtOAc and hexane and filtered to yield more of the title compound (0.67 g). Total yield (1.46 g, 60.7%). EI-MS m/z 294 (M+H+) Rt (1.37 min).

Big data shows that 22766-68-3 is playing an increasingly important role.

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

With the rapid development and complex challenges of chemical substances, new drug synthesis pathways are usually the most effective.22766-68-3,Ethyl quinuclidine-4-carboxylate,as a common compound, the synthetic route is as follows.

1 Azabicyclo 2.2.2Joct-4 yl(diphe yl)methanol ;A solution of phenyllithium (1.5-1.7 M in 70 cyclohexane / 30 ether, 20.0 mL, 32 mmol) was chilled down to -30 C under Ar. Ethyl 1-azabicyclo[2.2.2]octane-4- carboxylate (1.51g, 8.23 mmol) in THF (20 mL) was slowly added to the reaction mixture at -30 C over 25 min. The reaction was allowed to warm up to room temperature overnight. The reaction was quenched with H20 and then evaporated to dryness under vacuum. H20 and EtOAc were added, causing a white solid to crash out. This solid was filtered off, to give the title compound (0.79 g). The aqueous phase was further extracted with EtOAc, the combined organic layers were dried over MgS04, filtered, and concentrated under vacuum. The crude product was treated with EtOAc and hexane and filtered to yield more of the title compound (0.67 g). Total yield (1.46 g, 60.7%). EI-MS m/z 294 (M+H+) Rt (1.37 min).

22766-68-3 Ethyl quinuclidine-4-carboxylate 573424, aquinuclidine compound, is more and more widely used in various.

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

22766-68-3, Ethyl quinuclidine-4-carboxylate is a quinuclidine compound, ?involved in a variety of chemical synthesis. Rlated chemical reaction is continuously updated

Step 1. A solution of 4-carbethoxyquinuclidine (10.92 g) in THF (155 mL) was treated at-780C with borane-THF (1.0 M, 77.5 mL). The resulting mixture was stirred at -78C for 4 h, then treated with water (50 mL), warmed to room temperature and stirred for an additional hour. The reaction mixture was diluted with ethyl acetate and the aqueous phase was separated and extracted with two further portions of ethyl acetate. The combined organic layers were washed with brine- (twice), dried (MgSO4), filtered and evaporated in vacuo. Purification by silica gel chromatography (eluting with cyclohexane-ethyl acetate [1 :0 to 1 :1]) gave 1-boranyl-1-aza-bicyclo[2.2.2]octane-4- carboxylic acid ethyl ester (7.12 g, 61%) as an off-white solid. 1H NMR (400 MHz, CDCI3) delta 4.16 (2H1 q, J = 6.9), 3.10-3.05 (6H1 m), 1.98-1.93 (6H, m), 1.26 (3H, t, J = 6.9).

As the paragraph descriping shows that 22766-68-3 is playing an increasingly important role.

Reference£º
Patent; ARGENTA DISCOVERY LIMITED; WO2008/99186; (2008); A1;,
Quinuclidine – Wikipedia
Quinuclidine | C7H13N | ChemSpider