Category: 143557-91-9

These common heterocyclic compound, 143557-91-9, name is tert-Butyl 3-endo-3-hydroxy-8-azabicyclo[3.2.1]octane-8-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. Quality Control of tert-Butyl 3-endo-3-hydroxy-8-azabicyclo[3.2.1]octane-8-carboxylate

To a solution of (1R,3r,5S)-tert-butyl 3-hydroxy-8-azabicyclo[3.2.1]octane-8-carboxylate (9.0 g) in DCM (200 mL) was added TEA (11.0 mL) and MsCI (3.7 mL). Theresulting mixture was stirred at 0C for 2 hours, and then diluted with water (100 mL). The reaction mixture was extracted with DCM (2×200 mL). The combined organic layers were washed, dried and concentrated to afford (1 R,3r,5S)-tert-butyl 3-((methylsulfonyl)oxy)-8- azabicyclo[3.2.1]octane-8-carboxylate (12.0 g).

The synthetic route of tert-Butyl 3-endo-3-hydroxy-8-azabicyclo[3.2.1]octane-8-carboxylate has been constantly updated, and we look forward to future research findings.

Reference:
Patent; GLAXOSMITHKLINE INTELLECTUAL PROPERTY DEVELOPMENT LIMITED; CHEN, Weichun; IGBOKO, Ebere F; LIN, Xichen; LU, Hongfu; REN, Feng; WREN, Paul Bryan; XU, Zhongmiao; YANG, Ting; ZHU, Lingdong; WO2015/181186; (2015); A1;,
Amide – Wikipedia,
Amide – an overview | ScienceDirect Topics

Synthetic Route of 143557-91-9,Some common heterocyclic compound, 143557-91-9, name is tert-Butyl 3-endo-3-hydroxy-8-azabicyclo[3.2.1]octane-8-carboxylate, molecular formula is C12H21NO3, 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.

3alpha-Cyclopropylmethoxy-8-azabicyclo[3.2.1]octane-8-carboxylic acid t-butyl ester A reaction flask was charged with crude 3alpha-hydroxy-8-azabicyclo[3.2.1]octane-8-carboxylic acid t-butyl ester (5.5 g) in dry DMF (25 mL) under Argon. NaH (60% in oil, 0.968 g, 24.2 mmol) was added in portions and the mixture was stirred at 50 for 1 h. The mixture was cooled to rt and bromomethylcyclopropane (3.252 g, 24.2 mmol) was added followed by stirring at rt for 20 h under Argon. The reaction mixture was quenched with water and the product extracted into EtOAc. The combined organic phases were dried over Na2SO4, filtered, and concentrated. The product was purified by flash column chromatography (SiO2; n-heptane/EtOAc 2:1) to give the title compound (3.354 g). 1H NMR (CDCl3) delta 3.98-3.94 (m, 2H), 3.44-3.40 (m, 1H), 3.05 (d, 2H), 1.96-1.88 (m, 2H), 1.79-1.62 (m, 6H), 1.29 (s, 9H), 0.88-0.79 (m, 1H), 0.35-0.30 (m, 2H), 0.04-0.00 (m, 2H); 13C NMR (CDCl3) delta 153.4, 78.9, 73.0, 72.5, 52.7, 34.9, 28.5, 28.1, 10.9, 2.8.

The synthetic route of 143557-91-9 has been constantly updated, and we look forward to future research findings.

Reference:
Patent; ACADIA PHARMACEUTICALS, INC.; Skjaerbaek, Niels; Koch, Kristian Norup; Friberg, Bo Lennart Mikael; Tolf, Bo-Ragnar; (70 pag.)US9522906; (2016); B2;,
Amide – Wikipedia,
Amide – an overview | ScienceDirect Topics

Application of 143557-91-9, A common heterocyclic compound, 143557-91-9, name is tert-Butyl 3-endo-3-hydroxy-8-azabicyclo[3.2.1]octane-8-carboxylate, molecular formula is C12H21NO3, 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.

To a solution of tert-butyl (3-endo)-3-hyd roxy-8-azabicyclo[3.2.1 ]octane-8-carboxylate (3g, 13.20 mmol, combi-blocks) in THF (30 mL) was added portion wise potassium tertbutoxide (1.6 g, 14.5 mmol). The reaction was then refluxed for lh. The reaction was removed from the oil bath and 1-bromo-2,4-difluoro-benzene (1.6 mL, 14.52 mmol, Matrix) was added. The reaction was again refluxed for 1 .5h and cooled to RT. Ethyl acetate was added. The layers were separated and the organic layer was washed withwater, brine, dried over sodium sulphate, filtered and concentrated in vacuo. The crude was purified by flash chromatography using 5% ethyl acetate in cyclohexane to give a colourless oil that crystallised upon standing (4.1 g, 79%). 1H NMR (400 MHz, DMSOd 6): 67.63-7.59 (m, 1H), 6.98 (dd, J1= 11.40, J2= 2.76 Hz, 1H), 6.76-6.71 (m, 1H), 4.81 (t, J= 4.40 Hz, 1H), 4.06 (s, 2H), 2.15-2.05 (m, 4H), 1.87-1.84 (m, 4H), 1.41 (s, 9H).LCMS: (Method A) 344.0 (M-?Bu-f-H), Rt. 6.2 mm, 84.9% (Max).

The basis of chemical reaction formula synthesis, the synthesis route is composed of some specific reactions and combined according to certain logical thinking. We look forward to the emergence of more reaction modes in the future.

Reference:
Patent; ASCENEURON SA; QUATTROPANI, Anna; KULKARNI, Santosh S.; MURUGESAN, Kathiravan; BANERJEE, Joydeep; WO2014/198808; (2014); A1;,
Amide – Wikipedia,
Amide – an overview | ScienceDirect Topics

Researchers who often do experiments know that organic synthesis is a process of preparing more complex target molecules from simple raw materials through one or more chemical reactions. Generally, it requires fewer steps, and cheap raw materials. 143557-91-9, name is tert-Butyl 3-endo-3-hydroxy-8-azabicyclo[3.2.1]octane-8-carboxylate, A new synthetic method of this compound is introduced below., Safety of tert-Butyl 3-endo-3-hydroxy-8-azabicyclo[3.2.1]octane-8-carboxylate

General procedure: . Following GP1, under N2 atmosphere, to a 0C. solution of tert-butyl (1R,3r,5S)-3-hydroxybicyclo[3.2.1]octane-8-carboxylate (0.15 g, 1 eq., 0.66 mmol), phenol (0.07 g, 1.2 eq., 0.79 mmol), and PPh3 (0.21 mg, 1.5 eq., 0.99 mmol) in dry THF (5 mL) was added dropwise diisopropyl azodicarboxylate (0.2 mL, 1.2 eq., 0.79 mmol). The reaction crude was allowed to warm to room temperature and stirred for 16 h. Then, the mixture was quenched with HCl (10 mL) and extracted with EtOAc (25 mL). The organic extracts were washed with brine (10 mL), dried over Na2SO4 and concentrated in vacuo to furnish the crude product, which was purified by flash chromatography eluting with cyclohexane/EtOAc (0 to 80%) to give the pure title compound as colourless oil (0.07 g, 40%). UPLC-MS (method A): Rt. 1.86 min (TIC); ionization ES+304 [M+H]+. 1H NMR (400 MHz, DMSO-d6): delta 7.30-7.23 (m, 2H), 7.01-6.95 (m, 2H), 6.92 (td, J=7.3, 1.1Hz, 1H), 4.85-4.74 (m, 1H), 4.19-4.10 (m, 2H), 2.15-2.03 (m, 2H), 1.95-1.73 (m, 4H), 1.58-1.46 (m, 2H), 1.42 (s, 9H), 1.40-1.37 (m, 1H).

The basis of chemical reaction formula synthesis, the synthesis route is composed of some specific reactions and combined according to certain logical thinking. We look forward to the emergence of more reaction modes in the future.

Reference:
Patent; FONDAZIONE ISTITUTO ITALIANO DI TECNOLOGIA; BERTOZZI, Fabio; BANDIERA, Tiziano; PONTIS, Silvia; REGGIANI, Angelo; GIACOMINA, Francesca; DI FRUSCIA, Paolo; US2019/135778; (2019); A1;,
Amide – Wikipedia,
Amide – an overview | ScienceDirect Topics

Electric Literature of 143557-91-9, Each compound has different characteristics, and only by selecting the characteristics of the compound suitable for a specific situation can the compound be applied on a large scale. 143557-91-9, name is tert-Butyl 3-endo-3-hydroxy-8-azabicyclo[3.2.1]octane-8-carboxylate, This compound has unique chemical properties. The synthetic route is as follows.

Triphenylphosphine (3.57 g, 13.6 mmol) was solved in toluene (40 ml) and cooled to <;20C. Diethylazodicarboxylate (40% in toluene) (6.2 ml, 13.6 mmol) was added to the mixture below 20C, followed by stirring for 10 minutes, endo-3- Hydroxy-8-aza-bicyclo[3.2.1] octane-8-carboxylic acid te/t-butyl ester (2.58 g, 11.3 mmol) was added and after 10 minutes 7-hydroxy-3-methyl-chromen-2-one (2.0 g, 11.3 mmol) was added to the mixture. The temperature raised to 28C due to an exothermic reaction. The mixture was allowed to stir for 15 h at room temperature. Water (50 ml) and sodium hydroxide (20 ml, 0.1 M) was added followed by stirring. The mixture was filtered and washed with water and diethylether. Yield 2.50 g (57%). The chemical industry reduces the impact on the environment during synthesis tert-Butyl 3-endo-3-hydroxy-8-azabicyclo[3.2.1]octane-8-carboxylate. I believe this compound will play a more active role in future production and life. Reference:
Patent; NEUROSEARCH A/S; PETERS, Dan; NIELSEN, Elsebet, Østergaard; NIELSEN, Karin, Sandager; MUNRO, Gordon; WO2010/130620; (2010); A1;,
Amide – Wikipedia,
Amide – an overview | ScienceDirect Topics

Some common heterocyclic compound, 143557-91-9, name is tert-Butyl 3-endo-3-hydroxy-8-azabicyclo[3.2.1]octane-8-carboxylate, molecular formula is C12H21NO3, 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. HPLC of Formula: C12H21NO3

Compound I (4.23 g) was dissolved in DMF (100 mL), and thereto were added benzyl bromide (3.32 mL) and sodium hydride (1.62 g), and the mixture was stirred at room temperature overnight. To the reaction mixture was added water, and the mixture was extracted with diisopropylether. The organic layer was dried over sodium sulfate, and then concentrated under reduced pressure. The residue was purified by silica gel column chromatography (eluent: hexane/ethyl acetate=3/1) to give the title compound II (4.98 g).1H-NMR (CDCl3) delta1.47 (s, 9H), 1.93-2.05 (m, 6H), 2.13-2.19 (m, 2H), 3.72 (m, 1H), 4.12-4.26 (m, 2H), 4.49-4.50 (m, 2H), 7.26-7.30 (m, 1H), 7.32-7.41 (m, 4H)

These compound has a wide range of applications. It is believed that with the continuous development of the source of the synthetic route 143557-91-9, its application will become more common.

Reference:
Patent; DAINIPPON SUMITOMO PHARMA CO., LTD.; US2012/225876; (2012); A1;,
Amide – Wikipedia,
Amide – an overview | ScienceDirect Topics

These common heterocyclic compound, 143557-91-9, name is tert-Butyl 3-endo-3-hydroxy-8-azabicyclo[3.2.1]octane-8-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. Recommanded Product: 143557-91-9

To a solution of (1R,3r,5S)-tert-butyl 3-hydroxy-8-azabicyclo[3.2.1]octane-8-carboxylate (9.0 g) in DCM (200 mL) was added TEA (11.0 mL) and MsCI (3.7 mL). Theresulting mixture was stirred at 0C for 2 hours, and then diluted with water (100 mL). The reaction mixture was extracted with DCM (2×200 mL). The combined organic layers were washed, dried and concentrated to afford (1 R,3r,5S)-tert-butyl 3-((methylsulfonyl)oxy)-8- azabicyclo[3.2.1]octane-8-carboxylate (12.0 g).

The synthetic route of tert-Butyl 3-endo-3-hydroxy-8-azabicyclo[3.2.1]octane-8-carboxylate has been constantly updated, and we look forward to future research findings.

Reference:
Patent; GLAXOSMITHKLINE INTELLECTUAL PROPERTY DEVELOPMENT LIMITED; CHEN, Weichun; IGBOKO, Ebere F; LIN, Xichen; LU, Hongfu; REN, Feng; WREN, Paul Bryan; XU, Zhongmiao; YANG, Ting; ZHU, Lingdong; WO2015/181186; (2015); A1;,
Amide – Wikipedia,
Amide – an overview | ScienceDirect Topics

Electric Literature of 143557-91-9,Some common heterocyclic compound, 143557-91-9, name is tert-Butyl 3-endo-3-hydroxy-8-azabicyclo[3.2.1]octane-8-carboxylate, molecular formula is C12H21NO3, 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.

3alpha-Cyclopropylmethoxy-8-azabicyclo[3.2.1]octane-8-carboxylic acid t-butyl ester A reaction flask was charged with crude 3alpha-hydroxy-8-azabicyclo[3.2.1]octane-8-carboxylic acid t-butyl ester (5.5 g) in dry DMF (25 mL) under Argon. NaH (60% in oil, 0.968 g, 24.2 mmol) was added in portions and the mixture was stirred at 50 for 1 h. The mixture was cooled to rt and bromomethylcyclopropane (3.252 g, 24.2 mmol) was added followed by stirring at rt for 20 h under Argon. The reaction mixture was quenched with water and the product extracted into EtOAc. The combined organic phases were dried over Na2SO4, filtered, and concentrated. The product was purified by flash column chromatography (SiO2; n-heptane/EtOAc 2:1) to give the title compound (3.354 g). 1H NMR (CDCl3) delta 3.98-3.94 (m, 2H), 3.44-3.40 (m, 1H), 3.05 (d, 2H), 1.96-1.88 (m, 2H), 1.79-1.62 (m, 6H), 1.29 (s, 9H), 0.88-0.79 (m, 1H), 0.35-0.30 (m, 2H), 0.04-0.00 (m, 2H); 13C NMR (CDCl3) delta 153.4, 78.9, 73.0, 72.5, 52.7, 34.9, 28.5, 28.1, 10.9, 2.8.

The synthetic route of 143557-91-9 has been constantly updated, and we look forward to future research findings.

Reference:
Patent; ACADIA PHARMACEUTICALS, INC.; Skjaerbaek, Niels; Koch, Kristian Norup; Friberg, Bo Lennart Mikael; Tolf, Bo-Ragnar; (70 pag.)US9522906; (2016); B2;,
Amide – Wikipedia,
Amide – an overview | ScienceDirect Topics

Application of 143557-91-9, A common heterocyclic compound, 143557-91-9, name is tert-Butyl 3-endo-3-hydroxy-8-azabicyclo[3.2.1]octane-8-carboxylate, molecular formula is C12H21NO3, 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.

To a solution of tert-butyl (3-endo)-3-hyd roxy-8-azabicyclo[3.2.1 ]octane-8-carboxylate (3g, 13.20 mmol, combi-blocks) in THF (30 mL) was added portion wise potassium tertbutoxide (1.6 g, 14.5 mmol). The reaction was then refluxed for lh. The reaction was removed from the oil bath and 1-bromo-2,4-difluoro-benzene (1.6 mL, 14.52 mmol, Matrix) was added. The reaction was again refluxed for 1 .5h and cooled to RT. Ethyl acetate was added. The layers were separated and the organic layer was washed withwater, brine, dried over sodium sulphate, filtered and concentrated in vacuo. The crude was purified by flash chromatography using 5% ethyl acetate in cyclohexane to give a colourless oil that crystallised upon standing (4.1 g, 79%). 1H NMR (400 MHz, DMSOd 6): 67.63-7.59 (m, 1H), 6.98 (dd, J1= 11.40, J2= 2.76 Hz, 1H), 6.76-6.71 (m, 1H), 4.81 (t, J= 4.40 Hz, 1H), 4.06 (s, 2H), 2.15-2.05 (m, 4H), 1.87-1.84 (m, 4H), 1.41 (s, 9H).LCMS: (Method A) 344.0 (M-?Bu-f-H), Rt. 6.2 mm, 84.9% (Max).

The basis of chemical reaction formula synthesis, the synthesis route is composed of some specific reactions and combined according to certain logical thinking. We look forward to the emergence of more reaction modes in the future.

Reference:
Patent; ASCENEURON SA; QUATTROPANI, Anna; KULKARNI, Santosh S.; MURUGESAN, Kathiravan; BANERJEE, Joydeep; WO2014/198808; (2014); A1;,
Amide – Wikipedia,
Amide – an overview | ScienceDirect Topics

Researchers who often do experiments know that organic synthesis is a process of preparing more complex target molecules from simple raw materials through one or more chemical reactions. Generally, it requires fewer steps, and cheap raw materials. 143557-91-9, name is tert-Butyl 3-endo-3-hydroxy-8-azabicyclo[3.2.1]octane-8-carboxylate, A new synthetic method of this compound is introduced below., HPLC of Formula: C12H21NO3

To a suspension of 60% sodium hydride dispersion (0.270 g, 6.75 mmol) in 20 mL DMSO, (lR,3r,5S)-tert-butyl 3-hydroxy-8-azabicyclo[3.2.1]octane-8-carboxylate (1.0 g, 4.399 mmol) was added. After stirring at room temperature for 20 min, l-(benzyloxy)-4-fluorobenzene (0.89 g, 4.401 mmol) was added and mixture was stirred at 90C (oil bath). After 2.5 d, dark mixture was extracted with water and AcOEt (3x). Combined organic phases were dried over MgS04, filtered, and concentrated. Residue (ca. 3 g) was dissolved in 40 mL CH2C12 and triethylamine (1 mL, 7.175 mmol) and di-teri-butyl dicarbonate (0.961 g, 4.401 mmol) were added. After 10 min, mixture was transferred into a separatory funnel and extracted with water and CH2C12. Organic phases was dried over MgSO/t, filtered, and concentrated. Residue was purified by Biotage column chromatography (Si02, hexane/ AcOEt gradient) to give (lR,3r,55)-teri-butyl 3-(4-(benzyloxy)phenoxy)-8- azabicyclo[3.2.1]octane-8-carboxylate (0.34 g, 0.830 mmol, 18.9%) as a white solid. Exact mass calculated for C25H31F6N04: 409.23, found: LCMS m/z = 410.2 [M+H]+; lU NMR (400 MHz, CDC13) delta ppm 1.47 (s, 9H), 1.93-1.97 (m, 4H), 2.07-2.17 (m, 4H), 4.49-4.53 (m, 2H), 4.50-4.52 (m, 1H), 5.01 (s, 2H), 6.75-6.77 (m, 2H), 6.89-6.91 (m, 2H), 7.31-7.43 (m, 5H).

The basis of chemical reaction formula synthesis, the synthesis route is composed of some specific reactions and combined according to certain logical thinking. We look forward to the emergence of more reaction modes in the future.

Reference:
Patent; ARENA PHARMACEUTICALS, INC.; JONES, Robert M.; BUZARD, Daniel J.; HAN, Sangdon; KIM, Sun Hee; LEHMANN, Juerg; ZHU, Xiuwen; WO2013/55910; (2013); A1;,
Amide – Wikipedia,
Amide – an overview | ScienceDirect Topics