Category: 189333-49-1

189333-49-1, 3-Benzyl-3,9-diazaspiro[5.5]undecane is a piperidines compound, ?involved in a variety of chemical synthesis. Rlated chemical reaction is continuously updated

3-Benzyl-3,9-diazaspiro[5.5]undecane (6.14 mmol) is dissolved in 2.5% acetic acid in DCM (24 mL) at 0 C. and treated dropwise with cyclobutanone (9.21 mmol). The mixture is stirred for 30 min and then sodium triacetoxyborohydride (9.21 mmol) is added in portions. The reaction mixture is stirred at rt overnight, basified with saturated sodium carbonate solution and extracted with DCM. The combined extracts are washed with water, and then brine, dried over anhydrous Na2SO4 and concentrated in vacuo to afford the title compound. LC-MS (Method 1)=299.19; RT=1.26 min., 189333-49-1

The synthetic route of 189333-49-1 has been constantly updated, and we look forward to future research findings.

Reference：
Patent; Xu, Yuelian; Caldwell, Timothy M.; Xie, Linghong; Chenard, Bertrand L.; US2008/247964; (2008); A1;,
Piperidine – Wikipedia
Piperidine | C5H11N – PubChem

189333-49-1, 3-Benzyl-3,9-diazaspiro[5.5]undecane is a piperidines compound, ?involved in a variety of chemical synthesis. Rlated chemical reaction is continuously updated

Preparation of compound 2The mixture of the compound 1 (2.44 g) (US6291469, page 62, column 123), BoC2O (2 g) in MeOH (30 mL) was stirred overnight. After evaporation, the residue was purified by column to give the compound 2 (3 g, 87%).

189333-49-1, As the paragraph descriping shows that 189333-49-1 is playing an increasingly important role.

Reference：
Patent; ASTRAZENECA AB; WO2007/30061; (2007); A1;,
Piperidine – Wikipedia
Piperidine | C5H11N – PubChem

With the rapid development and complex challenges of chemical substances, new drug synthesis pathways are usually the most effective.189333-49-1,3-Benzyl-3,9-diazaspiro[5.5]undecane,as a common compound, the synthetic route is as follows.

Example Bl a.; Preparation of final compound 1; A mixture of intermediate compound 3 (prepared according to Al.c) (0.02 mol), 3- (phenylmethyl)-3,9-diazaspiro-[5.5]-undecane (0.02 mol) and Ti(iPrO)4 (0.035 mol) in 1,2-dichloroethane (80 ml) was stirred at 50C for a overnight, then brought to room temperature under N2 flow. NaBH(OAc)3 (0.035 mol) was added portionwise. The mixture was stirred at room temperature for 8 hours and poured out on ice. K2C03 10% was added. The mixture was filtered over celite and washed with CH2C12. The filtrate was extracted with CH2Cl2. The organic layer was separated, dried (MgS04), filtered, and the solvent was evaporated. The residue (26 g) was purified by column chromatography over silica gel (eluent gradient: CH2Cl2/CH3OH/NH4OH 95/5/0.5 to 90/10/1; 20-45 mum). Three fractions were collected and the solvent was evaporated. Yield: 1.8 g of final’compound 1 (15 %).

189333-49-1, As the paragraph descriping shows that 189333-49-1 is playing an increasingly important role.

Reference：
Patent; JANSSEN PHARMACEUTICA N.V.; WO2005/97795; (2005); A1;,
Piperidine – Wikipedia
Piperidine | C5H11N – PubChem

With the rapid development and complex challenges of chemical substances, new drug synthesis pathways are usually the most effective.189333-49-1,3-Benzyl-3,9-diazaspiro[5.5]undecane,as a common compound, the synthetic route is as follows.

To 5-fluoro-2-nitroanisole (1.0 kg, 5.84 mol, 1 equivalent) and3-Benzyl-3,9-diaza-spiro [5.5] undecane (1.70 kg, 5.57 mol, 0.95 equivalent)After adding N, N-diisopropylethylamine (1.13 kg, 8.77 mol, 1.55 equivalents) to a solution of N-methylpyrrolidone (4 L), the reaction solution was stirred at 100 C for 4 hours.TLC (dichloromethane: methanol = 6: 1, Rf = 0.5) showed that the reaction was complete. After the reaction solution was cooled to room temperature, water (16L) was slowly added to the reaction solution, and a large amount of solids precipitated. The suspension was stirred for 1 hour and then filtered. The filter cake was added to ethanol (5L), and refluxed for 1 hour.After cooling to room temperature, it was filtered. After the filter cake was re-slurried with ethanol (5L) under reflux,It was then filtered and the filter cake was dried to give the product (1.92 kg, 83% yield) as a yellow solid.

189333-49-1, The synthetic route of 189333-49-1 has been constantly updated, and we look forward to future research findings.

Reference：
Patent; Qilu Pharmaceutical Co., Ltd.; Lin Dong; Zhou Guangqiang; Li Shubin; Wang Xin; Zhang Zhantao; Liu Zhen; Wang Xinsheng; (30 pag.)CN110407877; (2019); A;,
Piperidine – Wikipedia
Piperidine | C5H11N – PubChem

189333-49-1, 3-Benzyl-3,9-diazaspiro[5.5]undecane is a piperidines compound, ?involved in a variety of chemical synthesis. Rlated chemical reaction is continuously updated

To 5 – fluoro -2 – nitroanisole (1.0 kg, 5 . 84 muM, 1 equivalent) and 3 – benzyl – 3, 9 – diaza spiro [5.5] undecane (1.70 kg, 5 . 57 muM, 0 . 95 equivalent) of N – methyl pyrrolidone (4 L) are added in the solution of the N, N – diisopropyl serotonin reuptake (1.13 kg, 8 . 77 muM, 1 . 55 equivalent) in the reaction liquid after 100 C under stirring for 4 hours. TLC (dichloromethane: methanol=6:1, Rf=0.5) display the reaction is complete. After the reaction cooled to room temperature water (16 L) is slowly added to the reaction solution, a large number of solid precipitation, suspension to continue stirring 1 hour after-filtration, the filter cake is added to ethanol (5 L) in, reflux beating 1 hour, cooling to room temperature and filtered. The flotation cake re-ethanol (5 L) reflux beating, then filtered, the filter cake drying to obtain the product (1.92 kg, 83% yield) as a yellow solid.

189333-49-1, As the paragraph descriping shows that 189333-49-1 is playing an increasingly important role.

Reference：
Patent; Qilu Pharmaceutical Co., Ltd.; Ding Zhaozhong; Chen Shuhui; Liu Xile; Wan Haiwen; Zhang Lu; (27 pag.)CN106928275; (2017); A;,
Piperidine – Wikipedia
Piperidine | C5H11N – PubChem

With the rapid development and complex challenges of chemical substances, new drug synthesis pathways are usually the most effective.189333-49-1,3-Benzyl-3,9-diazaspiro[5.5]undecane,as a common compound, the synthetic route is as follows.

Triethylamine (5.80 g, 57.29 mmol, 7.94 mL) and 4-dimethylaminopyridine (174.97 mg, 1.43 mmol) were slowly added into compound I2-A (3.50 g, 14.32 mmol) and Boc-anhydride (4.69 g, 21.48 mmol, 4.94 mL) in THF solution (40.00 mL) at r.t., the reaction mixture was stirred at 40C for 12 hours, then heated to 55C and stirred for 18 hours. The crude compound was concentrated up to dryness, purified by silica gel column (PE/EtOAc =6:1, 4:1) to give the compound I2-B. MS m/z: 345.5 [M+H]+

189333-49-1, The synthetic route of 189333-49-1 has been constantly updated, and we look forward to future research findings.

Reference：
Patent; Shijiazhuang Sagacity New Drug Development Co., Ltd.; QIAN, Wenyuan; YANG, Chundao; LI, Zhengwei; LI, Jie; LI, Jian; CHEN, Shuhui; (137 pag.)EP3572413; (2019); A1;,
Piperidine – Wikipedia
Piperidine | C5H11N – PubChem

With the rapid development and complex challenges of chemical substances, new drug synthesis pathways are usually the most effective.189333-49-1,3-Benzyl-3,9-diazaspiro[5.5]undecane,as a common compound, the synthetic route is as follows.

Sodium cyanoborohydride (1.3 g, 20 mmol) is added to a solution of 3-benzyi-3,9-diaza- spiro[5.5]undecane (980 mg, 4.01 mmol) and acetonitriie (20 mL) cooled to 0 0C. 37% Aqueous formaldehyde (9.5 mL) is added in one portion. After 5 min, glacial acetic acid (2.1 mL) is added in three portions over 1 h. After 20 h, the mixture is made basic with 1 M aqueous NaOH and then extracted with CH2CI2 (4 X 50 mL). The combined organic layers are dried over filtered, and concentrated. Purification by flash column chromatography (2% NH4OH in 4: 3 CH2C^MeOH, 75 g SiO2) affords the title compound as a pale yellow oil. LC-MS m/? (M + H+): 259.29 (§)., 189333-49-1

The synthetic route of 189333-49-1 has been constantly updated, and we look forward to future research findings.

Reference：
Patent; NEUROGEN CORPORATION; WO2007/140383; (2007); A2;,
Piperidine – Wikipedia
Piperidine | C5H11N – PubChem

189333-49-1, 3-Benzyl-3,9-diazaspiro[5.5]undecane is a piperidines compound, ?involved in a variety of chemical synthesis. Rlated chemical reaction is continuously updated

EXAMPLE 6. PREPARATION OF DIHYDROCHLORIDE OF 3-BENZYL-S5Q-DIAZASPIRO[S-S]UNDECANEThis Example illustrates the preparation of the dihydrochloride of 3-benzyl-3,9- diazaspiro [5.5]undecane : Crude 3-benzyl-3,9-diazaspiro[5.5]undecane (52.31 g, 0.214 mol) is dissolved in EtOH (157 mL) under nitrogen to form a clear Solution A. Concentrated HCl solution (36%, 43.36 g, 0.428 mol) is diluted in EtOH (173 mL) and the solution is cooled to 10 0C with an ice/water bath for form Solution B. Solution A is added slowly to Solution B while stirring under nitrogen. The resulting suspension is stirred at 10 0C for 1 h. The formed solid is filtered and washed with acetone (200 mL) and then tert-butyl methyl ether (200 mL). The solid is air-dried to give the title compound as a white powder (42.9 g, 63.2% overall yield for reduction and salt formation steps). LC-MS (M+l) 245.12; Rtau = 1.54 min. 1H NMR (CD3OD) 1.68-1.72 (m, 4H), 1.94-2.02 (m, 4H), 3.20-3.28 (m, 5H), 3.30- 3.40 (m, 6H), 4.36 (s, IH), 7.49-7.56 (m, 5H)., 189333-49-1

The synthetic route of 189333-49-1 has been constantly updated, and we look forward to future research findings.

Reference：
Patent; NEUROGEN CORPORATION; XU, Yuelian; XIE, Linghong; HAN, Bingsong; MAYNARD, George D.; CHENARD, Bertrand, L.; STAAB, Andrew J.; WO2009/97405; (2009); A2;,
Piperidine – Wikipedia
Piperidine | C5H11N – PubChem

With the rapid development and complex challenges of chemical substances, new drug synthesis pathways are usually the most effective.189333-49-1,3-Benzyl-3,9-diazaspiro[5.5]undecane,as a common compound, the synthetic route is as follows.

EXAMPLE 5. PREPARATION OF HEMI FUMARATE OF 3-BENZYL-S^-DIAZASPIRO[S-S]UNDECANEThis Example illustrates the preparation of the hemi fumarate of 3-benzyl-3,9- diazaspiro [5.5]undecane :Crude 3-benzyl-3,9-diazaspiro[5.5]undecane (72.1 g, 0.295 mol) (from Example 4) is suspended in wo-propanol (200 mL) and heated at 65 0C under nitrogen to form a clear Solution B. Fumaric acid (17. Ig, 0.147 mol) is suspended in wo-propanol (190 mL) and reflux to form a clear Solution A. Solution A is added to Solution B in one portion while stirring under nitrogen. The resulting clear solution becomes cloudy in a minute and more precipitate forms. The heat bath is removed and resulting mixture is stirred overnight under nitrogen. The mixture is filtered under nitrogen and washed with small amount of wo-propanol (-60 mL). The product is dried under high vacuum to give the title compound as a white loose powder. 74.5 g (yield 83.5%, and overall yield in 76%). LC-MS (M+l) 245.12; Rtau = 1.54 min. 1H NMR (CD3OD) 1.60-1.72 (m, 8H), 2.50-2.60 (m, 4H), 3.10-3.16 (m, 4H), 3.64 (s, 2H), 6.64 (s, IH), 7.26-7.38 (m, 5H).

189333-49-1, As the paragraph descriping shows that 189333-49-1 is playing an increasingly important role.

Reference：
Patent; NEUROGEN CORPORATION; XU, Yuelian; XIE, Linghong; HAN, Bingsong; MAYNARD, George D.; CHENARD, Bertrand, L.; STAAB, Andrew J.; WO2009/97405; (2009); A2;,
Piperidine – Wikipedia
Piperidine | C5H11N – PubChem

189333-49-1, 3-Benzyl-3,9-diazaspiro[5.5]undecane is a piperidines compound, ?involved in a variety of chemical synthesis. Rlated chemical reaction is continuously updated

b. Preparation of final compound 5; A mixture of intermediate compound 3 (prepared according to Al.c) (0.033 mol), 3- (phenylmethyl)-3,9-diazaspiro-[5.5]-undecane (0.033 mol), Ti (iPrO)4 mol) and Pd/C (1.5 g) in thiophene (1 ml) and methanol (150 ml) was hydrogenated at 50C for 18 hours under a 5 bar pressure, then filtered over celite. Celite was washed with CH30H. The filtrate was evaporated till dryness. The residue was dissolved in CH2C12. K2C03 10 % was added. The mixture was stirred at room temperature for 30 minutes, then filtered over celite. Celite was washed with CH2C12. The filtrate was extracted with CH2C12. The organic layer was separated, dried (MgS04), filtered, and the solvent was evaporated. The residue (20 g) was purified by column chromatography over silica gel (eluent: CH2Cl2/CH3OH/NH4OH 94/6/0.5; 20-45 mum). Two fractions were collected and the solvent was evaporated. The residue was dissolved in iPrOH and converted into the hydrochloric acid salt. The precipitate was filtered off and dried. Yield: 3.5 g of final compound 5 (14 %) (melting point: 183C).

189333-49-1, The synthetic route of 189333-49-1 has been constantly updated, and we look forward to future research findings.

Reference：
Patent; JANSSEN PHARMACEUTICA N.V.; WO2005/97795; (2005); A1;,
Piperidine – Wikipedia
Piperidine | C5H11N – PubChem