Category: 768-66-1

768-66-1, 2,2,6,6-Tetramethylpiperidine is a piperidines compound, ?involved in a variety of chemical synthesis. Rlated chemical reaction is continuously updated,768-66-1

Experimental Section: Preparation of the reagent TMPMgCl·LiCl (5b): ; A dry and argon flushed 250 mL flask, equipped with a magnetic stirrer and a septum, was charged with freshly titrated i-PrMgCl·LiCl (100 mL, 1.2 M in THF, 120 mmol). 2,2,6,6-tetramethylpiperidine (TMPH) (19.8 g, 126 mmol, 1.05 equiv) was added dropwise at room temperature. The reaction mixture was stirred until gas evaluation was completed (ca. 24 h) at room temperature.

The synthetic route of 768-66-1 has been constantly updated, and we look forward to future research findings.

Reference：
Patent; Ludwig-Maximilians-Universitaet Muenchen; EP1810974; (2007); A1;,
Piperidine – Wikipedia
Piperidine | C5H11N – PubChem

768-66-1, 2,2,6,6-Tetramethylpiperidine is a piperidines compound, ?involved in a variety of chemical synthesis. Rlated chemical reaction is continuously updated,768-66-1

A solution of 2,2,6,6-tetramethyl-4-piperidine (TMP) (45 mL, 267 mmol) in THF (400 mL) was cooled to -78 C. under an atmosphere of nitrogen. n-Butyl lithium (2.5 M in hexane, 110 mL, 275 mmol) was added slowly maintaining the temperature below -70 C. After addition, the reaction mixture was warmed to -50 C. and stirred for 30 minutes. The clear solution became turbid indicating the salt formation. The reaction mixture was recooled to -80 C., and a solution of 2-fluoro-4-methylbenzonitrile (32.4 g, 240 mmol) in THF (150 mL) was slowly added maintaining temperature below -70 C. The mixture was then warmed to -50 C. and stirred for 30 minutes. The mixture was recooled to -70 C. and a saturated solution of iodine (67 g, 264 mmol) in THF (150 mL) was added slowly maintaining the temperature at -70 C. After addition, the mixture was warmed to ambient temperature. The reaction mixture was poured into a solution of Na2S2O3 (160 g in 1.5 L of water) and stirred for 1 h. The organic layer was separated, and the aqueous layer was extracted with ethyl acetate. The organic layers were combined, washed with brine, dried over Na2SO4, and filtered. The volatiles were evaporated under reduced pressure. The crude product was subjected to vacuum distillation, and at about 60 C., the excess TMP was removed, at about 100 C., the starting compound 2-fluoro-4-methylbenzonitrile and a small amount of 2-fluoro-3-iodo-4-methylbenzonitrile were removed and, finally at 115 C., pure 2-fluoro-3-iodo-4-methylbenzonitrile was obtained as an off-white amorphous solid. MS (ESI, pos. ion) m/z: 261.9 (M+1).

The synthetic route of 768-66-1 has been constantly updated, and we look forward to future research findings.

Reference：
Patent; Amgen Inc.; US2006/199817; (2006); 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.768-66-1,2,2,6,6-Tetramethylpiperidine,as a common compound, the synthetic route is as follows.

A solution of n-BuLi (12.4 ml, 30.9 mmol, 2.5M in hexane) was added to a solution of 2,2,6,6-tetramethylpiperidine (4.8 g, 33.7 mmol) in 35 ml THF at 0 C. to form LTMP. In a separate flask, a solution of the product of step 2 (4.5 g, 14.04 mmol) and dibromomethane (5.3 g, 30.9 mmol) in 30 ml of THF was cooled to -70 C. After 30 min, LTMP solution was cooled to -70 C., and added to above solution via a cannula over 30 min at -65 C. After 10 min, a solution of lithium bis(trimethyl)silyl amide solution (28 ml, 28 mmol, 1M in THF) was added over 15 min at -70 C. The resulting mixture was allowed to warm to -20 C. and then cooled back to -70 C. A solution of s-BuLi solution (43.2 ml, 56.2 mmol, 1.3 M in cyclohexane) was added at -60 C. over 15 min. The mixture was allowed to warm to room temperature. A solution of n-BuLi (12.4 ml, 28 mmol, 2.5 in hexane) was added to the reaction, and the reaction was stirred at room temperature for 1 h. The reaction was cooled to -70 C. and transferred into an acidic ethanol solution (15 ml acetyl chloride and 75 ml ethanol) at 0 C. via a cannula over 1 h. The resulting mixture was diluted with 280 ml ether and washed with 280 ml 10% HCl solution. The aqueous layer was extracted with ether. The combined organic layer was washed with brine, dried with MgSO4, and concentrated. The residue was purified by chromatography (on silica gel, ethyl acetate/hexane=5/95) to give a brown liquid in 1.65 g. NMR spectra of the product were consistent for the proposed structure., 768-66-1

As the paragraph descriping shows that 768-66-1 is playing an increasingly important role.

Reference：
Patent; Nagarajan, Srinivasan R.; Khanna, Ish Kumar; Clare, Michael; Gasiecki, Alan; Rogers, Thomas; Chen, Barbara; Russell, Mark; Lu, Hwang-Fun; Yi, Yu; Huff, Renee M.; Desai, Bipinchandra N.; Devadas, Balekudru; Parikh, Mihir D.; Penning, Thomas; US2004/92538; (2004); A1;,
Piperidine – Wikipedia
Piperidine | C5H11N – PubChem

768-66-1, 2,2,6,6-Tetramethylpiperidine is a piperidines compound, ?involved in a variety of chemical synthesis. Rlated chemical reaction is continuously updated

768-66-1, To a stirred, cooled (0 C) solution of 2,2,6,6-tetramethylpiperidine(0.50 mL, 3.0 mmol) in THF (5 mL) was added BuLi(about 1.6 M hexanes solution, 3.0 mmol). After 15 min at 0 C,ZnCl2TMEDA (0.25 g, 1.0 mmol) was added, and the mixture wasstirred for 15 min at this temperature before introduction of thesubstrate (2.0 mmol). After 2 h at room temperature, a solutionof I2 (0.74 g, 3.0 mmol) in THF (5 mL) was added. The mixturewas stirred overnight before addition of an aqueous saturated solutionof Na2S2O3 (10 mL) and extraction with CH2Cl2 (3 20 mL).The combined organic layers were dried over Na2SO4 and concentratedunder reduced pressure before purification by flash chromatographyon silica gel.

The synthetic route of 768-66-1 has been constantly updated, and we look forward to future research findings.

Reference：
Article; Nagaradja, Elisabeth; Bentabed-Ababsa, Ghenia; Scalabrini, Mathieu; Chevallier, Floris; Philippot, Stephanie; Fontanay, Stephane; Duval, Raphael E.; Halauko, Yury S.; Ivashkevich, Oleg A.; Matulis, Vadim E.; Roisnel, Thierry; Mongin, Florence; Bioorganic and Medicinal Chemistry; vol. 23; 19; (2015); p. 6355 – 6363;,
Piperidine – Wikipedia
Piperidine | C5H11N – PubChem

With the rapid development and complex challenges of chemical substances, new drug synthesis pathways are usually the most effective.768-66-1,2,2,6,6-Tetramethylpiperidine,as a common compound, the synthetic route is as follows.,768-66-1

A dry and nitrogen-flushed Schlenk flask equipped with a magnetic stirring bar and rubber septum was charged with iPrMgCl·LiCl (1.0 M in THF, 20 mL 20 mmol). Then, 2,2,6,6-tetramethylpiperidine (3.52 mL, 21 mmol) was added dropwise through a syringe within 5 min. The mixture was stirred until the gas evolution ceased (24-48 h). Titration against benzoic acid in THF (0 C) in the presence of 4-(phenylazo)diphenylamine as the indicator showed that the base concentration ranged from 0.9 to 0.98 M.

The synthetic route of 768-66-1 has been constantly updated, and we look forward to future research findings.

Reference：
Article; Bozzini, Leandro A.; Batista, Joao H.C.; de Mello, Murilo B.M.; Vessecchi, Ricardo; Clososki, Giuliano C.; Tetrahedron Letters; vol. 58; 44; (2017); p. 4186 – 4190;,
Piperidine – Wikipedia
Piperidine | C5H11N – PubChem

768-66-1, 2,2,6,6-Tetramethylpiperidine is a piperidines compound, ?involved in a variety of chemical synthesis. Rlated chemical reaction is continuously updated

General procedure: Catalyst [CuCl{2,5-bis(2-thiophenyl)phosphole}2] (1) (2.6 mg, 0.003 mmol, 0.1 mol%), paraformaldehyde (3.0 mmol), amine (3.3 mmol), phenylacetylene (4.5 mmol) and chlorobenezene (1 mL) were loaded in a screw-cap test tube equipped with a stirring bar. The mixture was stirred at 100 C for 5 h, cooled, extracted with ether (3×5 mL) and dried over MgSO4. The mixture was filtrated, concentrated and the residue was purified by flash chromatography on silica gel using a hexane/EtOAc mixture as eluent. The corresponding propargylamines were obtained as yellow oil. Reported yields are the average of at least two independent runs., 768-66-1

The synthetic route of 768-66-1 has been constantly updated, and we look forward to future research findings.

Reference：
Article; Cammarata, Jose Ricardo; Rivera, Rocio; Fuentes, Franmerly; Otero, Yomaira; Ocando-Mavarez, Edgar; Arce, Alejandro; Garcia, Juan M.; Tetrahedron Letters; vol. 58; 43; (2017); p. 4078 – 4081;,
Piperidine – Wikipedia
Piperidine | C5H11N – PubChem

768-66-1, 2,2,6,6-Tetramethylpiperidine is a piperidines compound, ?involved in a variety of chemical synthesis. Rlated chemical reaction is continuously updated

Preparation 33A: (3-Bromo-2-fluorophenyl)(pyridazin-3-yl)methanol[00195] A solution of LTMP was prepared by reaction of 2,2,6,6-tetramethylpiperidine (0.151 mL, 0.896 mmol) in THF (5.6 mL) and n-butyllithium (0.358 mL, 0.896 mmol) at -30 C and then at 0 C for 30 min., 768-66-1

768-66-1 2,2,6,6-Tetramethylpiperidine 13035, apiperidines compound, is more and more widely used in various fields.

Reference：
Patent; BRISTOL-MYERS SQUIBB COMPANY; BALOG, James Aaron; HUANG, Audris; VELAPARTHI, Upender; LIU, Peiying; WO2013/49263; (2013); A1;,
Piperidine – Wikipedia
Piperidine | C5H11N – PubChem

768-66-1,768-66-1, 2,2,6,6-Tetramethylpiperidine is a piperidines compound, ?involved in a variety of chemical synthesis. Rlated chemical reaction is continuously updated

“BuLi (1.6 M solution in hexanes, 11.3 ml_) was added dropwise over 15 min to a solution of 2,2,6,6-tetramethylpiperidine (TMPH) (3.0 mL, 18 mmol) in 20 ml_ of hexanes at 0 C. After addition, formation of white precipitate was observed. The resulting mixture was stirred at 0 C for 30 min, warmed up to room temperature and stirred for additional 1 h. All volatiles were pumped off. The product was precipitated from pentane (30 mL) at -30 C, filtered off and dried in vacuum (1.48 g, 56%). 1H NMR (400 MHz; THF-d8; delta, ppm): 1.07 (br s, 12H); 1.20 (br m, 4H); 1.65 (br m, 2H). 3C{1H} NMR (100.6 MHz; THF-d8; delta, ppm): 36.4 (br s); 42.9 (br s); /joso-carbon and one CH2 were not observed due to broadening. 7Li NMR (155.5 MHz; THF-de; delta, ppm): -0.5 (br s).

As the paragraph descriping shows that 768-66-1 is playing an increasingly important role.

Reference：
Patent; UTI LIMITED PARTNERSHIP; PIERS, Warren Edward; KHALIMON, Andrey Yur’evich; VON MARWITZ, Adam John; WO2013/142956; (2013); A1;,
Piperidine – Wikipedia
Piperidine | C5H11N – PubChem

768-66-1, 2,2,6,6-Tetramethylpiperidine is a piperidines compound, ?involved in a variety of chemical synthesis. Rlated chemical reaction is continuously updated

768-66-1, 2,2,6,6-tetramethylpiperidine (7.20 kg, 51.1 mol, 3.0 eq., KF=0.30%) was added into a 100 L reactor equipped with a temperature probe and overhead stirrer and mixed at RT under nitrogen protection. THF (50 L) was added into the reactor and stirred. The vessel was purged with nitrogen three times and cooled to 0 C. n-BuLi (20.4 L, 3.0 eq.; 2.5 M hexane solution) was added to the mixture dropwise while keeping the temperature at about 0 C to about 5 C for over one hour. The color of the solution turned yellow. The mixture was stirred at about 0 C to about 5 C for 30 minutes. The mixture was cooled to about -78 C to about -70 C to form Solution A.

As the paragraph descriping shows that 768-66-1 is playing an increasingly important role.

Reference：
Patent; HELSINN THERAPEUTICS (US) INC; HELSINN HEALTHCARE SA; HELSINN ADVANCED SYNTHESIS SA; RUBIO, Silvina Garcia; PERSEGHINI, Mauro; GUAINAZZI, Angelo; PIETRA, Claudio; GIULIANO, Claudio; (110 pag.)WO2019/118298; (2019); A1;,
Piperidine – Wikipedia
Piperidine | C5H11N – PubChem

768-66-1,With the rapid development and complex challenges of chemical substances, new drug synthesis pathways are usually the most effective.768-66-1,2,2,6,6-Tetramethylpiperidine,as a common compound, the synthetic route is as follows.

Step 1. Preparation of the tetramethylpiperidide solution. 1.9 mL (11.7 mmol; 3 eq. ) of 2,2, 6,6-tetramethylpiperidine was dissolved in 4 mL of anhydrous THF; the solution was cooled TO-80C and then 3.9 mL (9.8 mmol; 2.5 eq) of a 2.5 M solution BuLi in Hexane were added. The mixture was stirred for 2h at 0C.Step 1. Preparation of the tetramethylpiperidide solution. 1.9 mL (11.7 mmol; 3 eq. ) of 2,2, 6,6-tetramethylpiperidine was dissolved in 3 mL of anhydrous THF; the solution was cooled TO-80C and then 3.9 mL (9.8 mmol; 2.5 eq) of a 2.5 M solution BuLi in Hexane were added. The mixture was stirred for 2h at 0C.

The synthetic route of 768-66-1 has been constantly updated, and we look forward to future research findings.

Reference：
Patent; SIGMA-TAU INDUSTRIE FARMACEUTICHE RIUNITE S.p.A.; WO2005/7603; (2005); A2;,
Piperidine – Wikipedia
Piperidine | C5H11N – PubChem