Category: 278788-66-2

With the rapid development and complex challenges of chemical substances, new drug synthesis pathways are usually the most effective.278788-66-2,(R)-tert-Butyl 3-(hydroxymethyl)piperazine-1-carboxylate,as a common compound, the synthetic route is as follows.

Imidazole (30.2 g, 444 mmol) was taken up in 240 mL of DCM and chilled to 0 C. Thionyl chloride (9.76 mL, 134 mmol) was added slowly to the mixture. After 5 min, the mixture was warmed to room temperature and stirred for 1 h. The mixture was then cooled to -78 C. t-Butyl (3R)-3- (hydroxymethyl)-l-piperazinecarboxylate (10.33 g, 47.8 mmol, Tetrahedron, 2007, 63, 3057-3065) was added dropwise in 240 mL of DCM via addition funnel. The mixture was then warmed to room temperature and stirred for 18 h. The mixture was quenched with 200 mL of aq. NH4C1 and diluted with 200 mL of water. The mixture was partitioned and the aqueous portion was extracted with 200 mL of DCM. The combined organic extracts were dried over MgS04. Filtration and concentration under reduced pressure afforded tert-butyl (3ai?)tetrahydro[l,2,3]oxathiazolo[3,4-a]pyrazine-5(3H)-carboxylate 1-oxide (12.23 g) as a white solid.

278788-66-2, 278788-66-2 (R)-tert-Butyl 3-(hydroxymethyl)piperazine-1-carboxylate 24820286, apiperazines compound, is more and more widely used in various fields.

Reference：
Patent; AMGEN INC.; ASHTON, Kate; BOURBEAU, Matthew, Paul; HONG, Fang-Tsao; LIU, Longbin; NISHIMURA, Nobuko; NORMAN, Mark, H.; POON, Steve, F.; STEC, Markian, M.; ST. JEAN, David, J., JR; TAMAYO, Nuria, A.; YANG, Kevin, C.; WO2013/123444; (2013); A1;,
Piperazine – Wikipedia
Piperazines – an overview | ScienceDirect Topics

With the rapid development and complex challenges of chemical substances, new drug synthesis pathways are usually the most effective.278788-66-2,(R)-tert-Butyl 3-(hydroxymethyl)piperazine-1-carboxylate,as a common compound, the synthetic route is as follows.

To a solution of imidazole (15.7 g, 231 mmol) in DCM (100 mL) was added SOCl 2 (8.25 g, 69.4 mmol, 5.03 mL) at 0° C. The reaction mixture was stirred at 15° C. for 1 hour. To the mixture was added tert-butyl (3R)-3-(hydroxymethyl)piperazine-1-carboxylate (5 g, 23.1 mmol) in DCM (100 mL) at -70° C. The reaction mixture was stirred at 15° C. for 12 hour. Upon completion, the reaction mixture was quenched by saturated NH 4Cl (100 mL) and separated, the aqueous layer was extracted with DCM (40 mL). The combined organic layers were washed with brine (20 mL), dried over Na 2SO 4, filtered and concentrated under vacuum to give tert-butyl (3aR)-1-oxo-3a,4,6,7-tetrahydro-3H-oxathiazolo[3,4-a]pyrazine-5-carboxyla- te (5.8 g, 22.1 mmol, 95.6% yield) as a brown solid., 278788-66-2

As the paragraph descriping shows that 278788-66-2 is playing an increasingly important role.

Reference：
Patent; Mirati Therapeutics, Inc.; Array BioPharma Inc.; Blake, James F.; Burgess, Laurence E.; Chicarelli, Mark Joseph; Christensen, James Gail; Cook, Adam; Fell, Jay Bradford; Fischer, John P.; Marx, Matthew Arnold; Mejia, Macedonio J.; Savechenkov, Pavel; Vigers, Guy P.A.; Smith, Christopher Ronald; Rodriguez, Martha E.; US2019/144444; (2019); A1;,
Piperazine – Wikipedia
Piperazines – an overview | ScienceDirect Topics

With the rapid development and complex challenges of chemical substances, new drug synthesis pathways are usually the most effective.278788-66-2,(R)-tert-Butyl 3-(hydroxymethyl)piperazine-1-carboxylate,as a common compound, the synthetic route is as follows.

To a solution of imidazole (15.7 g, 231 mmol) in DCM (100 mL) was added SOCl 2 (8.25 g, 69.4 mmol, 5.03 mL) at 0° C. The reaction mixture was stirred at 15° C. for 1 hour. To the mixture was added tert-butyl (3R)-3-(hydroxymethyl)piperazine-1-carboxylate (5 g, 23.1 mmol) in DCM (100 mL) at -70° C. The reaction mixture was stirred at 15° C. for 12 hour. Upon completion, the reaction mixture was quenched by saturated NH 4Cl (100 mL) and separated, the aqueous layer was extracted with DCM (40 mL). The combined organic layers were washed with brine (20 mL), dried over Na 2SO 4, filtered and concentrated under vacuum to give tert-butyl (3aR)-1-oxo-3a,4,6,7-tetrahydro-3H-oxathiazolo[3,4-a]pyrazine-5-carboxyla- te (5.8 g, 22.1 mmol, 95.6% yield) as a brown solid., 278788-66-2

As the paragraph descriping shows that 278788-66-2 is playing an increasingly important role.

Reference：
Patent; Mirati Therapeutics, Inc.; Array BioPharma Inc.; Blake, James F.; Burgess, Laurence E.; Chicarelli, Mark Joseph; Christensen, James Gail; Cook, Adam; Fell, Jay Bradford; Fischer, John P.; Marx, Matthew Arnold; Mejia, Macedonio J.; Savechenkov, Pavel; Vigers, Guy P.A.; Smith, Christopher Ronald; Rodriguez, Martha E.; US2019/144444; (2019); A1;,
Piperazine – Wikipedia
Piperazines – an overview | ScienceDirect Topics

With the rapid development and complex challenges of chemical substances, new drug synthesis pathways are usually the most effective.278788-66-2,(R)-tert-Butyl 3-(hydroxymethyl)piperazine-1-carboxylate,as a common compound, the synthetic route is as follows.

Imidazole (30.2 g, 444 mmol) was taken up in 240 mL of DCM and chilled to 0 C. Thionyl chloride (9.76 mL, 134 mmol) was added slowly to the mixture. After 5 min, the mixture was warmed to room temperature and stirred for 1 h. The mixture was then cooled to -78 C. t-Butyl (3R)-3- (hydroxymethyl)-l-piperazinecarboxylate (10.33 g, 47.8 mmol, Tetrahedron, 2007, 63, 3057-3065) was added dropwise in 240 mL of DCM via addition funnel. The mixture was then warmed to room temperature and stirred for 18 h. The mixture was quenched with 200 mL of aq. NH4C1 and diluted with 200 mL of water. The mixture was partitioned and the aqueous portion was extracted with 200 mL of DCM. The combined organic extracts were dried over MgS04. Filtration and concentration under reduced pressure afforded tert-butyl (3ai?)tetrahydro[l,2,3]oxathiazolo[3,4-a]pyrazine-5(3H)-carboxylate 1-oxide (12.23 g) as a white solid.

278788-66-2, 278788-66-2 (R)-tert-Butyl 3-(hydroxymethyl)piperazine-1-carboxylate 24820286, apiperazines compound, is more and more widely used in various fields.

Reference：
Patent; AMGEN INC.; ASHTON, Kate; BOURBEAU, Matthew, Paul; HONG, Fang-Tsao; LIU, Longbin; NISHIMURA, Nobuko; NORMAN, Mark, H.; POON, Steve, F.; STEC, Markian, M.; ST. JEAN, David, J., JR; TAMAYO, Nuria, A.; YANG, Kevin, C.; WO2013/123444; (2013); A1;,
Piperazine – Wikipedia
Piperazines – an overview | ScienceDirect Topics

278788-66-2, (R)-tert-Butyl 3-(hydroxymethyl)piperazine-1-carboxylate is a piperazines compound, ?involved in a variety of chemical synthesis. Rlated chemical reaction is continuously updated

Step D: tert-butyl (3R)-4-[2-(3-cyano-4-fluorophenyl)-2-oxoethyl]-3-(hydrox)’Ilethyl)piperazine-1-carboxylate; To a solution of5-(bromoacetyl)-2-fluorobenzonitrile (13.1 g, 0.054 mol) inDMF (160 mL) was added tert-butyl (3R)-3-(hydroxymethyl)piperazine-1-carboxylate (13.1 g,0.065 mol) and K2C03 (11.77 g, 0.075mol), and the mixture was stirred at RTfor 3 h. Themixture was washed with water, and extracted with EtOAc. The organic layer was washed withbrine, dried over Na2S04 and concentrated in vacuum to give the title compound which was used for the next step without further purification., 278788-66-2

As the paragraph descriping shows that 278788-66-2 is playing an increasingly important role.

Reference：
Patent; MERCK SHARP & DOHME CORP.; PASTERNAK, Alexander; BLIZZARD, Timothy; CHOBANIAN, Harry; DE JESUS, Reynalda; DING, Fa-Xiang; DONG, Shuzhi; GUDE, Candido; KIM, Dooseop; TANG, Haifeng; WALSH, Shawn; PIO, Barbara; JIANG, Jinlong; WO2013/28474; (2013); A1;,
Piperazine – Wikipedia
Piperazines – an overview | ScienceDirect Topics

278788-66-2, (R)-tert-Butyl 3-(hydroxymethyl)piperazine-1-carboxylate is a piperazines compound, ?involved in a variety of chemical synthesis. Rlated chemical reaction is continuously updated

Step D: (3S,9aR)-3-(3-Cyano-4-fluoro-2-methyl-phenyl)-3-hydroxy-hexahydro-pyrazino[2, 1-cli 1,4loxazine-8-carboxylic acid tert-butyl ester: Diisopropylethylamine (156 mL, 894 mmol)was added to a stirred, room temperature mixture of 3-(2-Bromo-acetyl)-6-fluoro-2-methyl-benzonitrile (176 g, 688 mmol) and (R)-4-N-Boc-2-hydroxymethyl-piperazine (149 g, 688 mmol)in THE (3500 mL) and the mixture was stirred at room temperature for 18 h. The reaction wasdiluted with 3 L EtOAc, washed 2x with 1500 mL 10% wlw NaHCO3 aqueous solution, dried over Mg504, filtered and concentrated. The residue was purified by column chromatography on silica gel (40-80% EtOAc/Hexanes, linear gradient), to provide the title compound, 278788-66-2

As the paragraph descriping shows that 278788-66-2 is playing an increasingly important role.

Reference：
Patent; MERCK SHARP & DOHME CORP.; PASTERNAK, Alexander; DEJESUS, Reynalda, Keh; FRIE, Jessica, L.; PIO, Barbara; TANG, Haifeng; WALSH, Shawn, P.; WO2014/99633; (2014); A2;,
Piperazine – Wikipedia
Piperazines – an overview | ScienceDirect Topics

With the rapid development and complex challenges of chemical substances, new drug synthesis pathways are usually the most effective.278788-66-2,(R)-tert-Butyl 3-(hydroxymethyl)piperazine-1-carboxylate,as a common compound, the synthetic route is as follows.

NEt3 (12.9 mL, 92.47 mmol) was added to tert-butyl (3R)-3-(hydroxymethyl)piperazine-1-carboxylate (10 g, 46.24 mmol), tert-butylchlorodimethylsilane (10.45 g, 69.35 mmol) and 4-dimethylaminopyridine (0.282 g, 2.31 mmol) in DCM (200 mL) at rt. The resulting suspension was stirred at rt for 16 h. The solvent was removed in vacuo. The crude product obtained was purified by flash silica chromatography (0 to 9% MeOH in DCM) to afford tert-butyl (3R)-3-({[tert-butyl(dimethyl)silyl]oxy}methyl)piperazine-1-carboxylate (15 g, 98%) as a pale yellow gum; 1H NMR (300 MHz, DMSO, 30 C.) 0.05 (6H, s), 0.89 (9H, s), 1.40 (9H, s), 2.27 (1H, s), 2.41 (1H, s), 2.48-2.54 (2H, m), 2.71 (1H, s), 2.78-2.90 (1H, m), 3.33-3.57 (2H, m), 3.74 (1H, d), 3.86-3.96 (1H, m).

278788-66-2, 278788-66-2 (R)-tert-Butyl 3-(hydroxymethyl)piperazine-1-carboxylate 24820286, apiperazines compound, is more and more widely used in various fields.

Reference：
Patent; ASTRAZENECA AB; Kettle, Jason Grant; Bagal, Sharanjeet; Robb, Graeme Richard; Smith, James Michael; Goldberg, Frederick Woolf; Cassar, Doyle Joseph; Feron, James Lyman; US2019/177338; (2019); A1;,
Piperazine – Wikipedia
Piperazines – an overview | ScienceDirect Topics

With the rapid development and complex challenges of chemical substances, new drug synthesis pathways are usually the most effective.278788-66-2,(R)-tert-Butyl 3-(hydroxymethyl)piperazine-1-carboxylate,as a common compound, the synthetic route is as follows.

Intermediate 78 tert-Butyl (3R)-4-(5-aminothiazolo[5,4-d]pyrimidin-7-yl)-3-(hydroxymethyl)-piperazine-1-carboxylate [0299] To a solution of Intermediate 4 (4.63 mmol) and (R)-3-(hydroxymethyl)-piperazine-1-carboxylic acid tert-butyl ester (1 g, 4.62 mmol) in DMF (20 mL) was added DIPEA (6.94 mmol). The reaction mixture was heated at 100 C. for 7 h, then cooled and stirred at room temperature for 2 days. The reaction mixture was concentrated in vacuo and partitioned between EtOAc and water. The organic layers were dried over sodium sulfate and concentrated again. The resulting orange oil was purified by column chromatography on silica gel, with a gradient of 1% increasing to 20% MeOH in DCM, to yield the title compound (0.42 g, 24.8%) as a yellow gummy solid. LCMS (ES+) 367.8 (M+H)+, RT 0.8 minutes (method 3)., 278788-66-2

The synthetic route of 278788-66-2 has been constantly updated, and we look forward to future research findings.

Reference：
Patent; Brookings, Daniel Christopher; Ford, Daniel James; Franklin, Richard Jeremy; Ghawalkar, Anant Ramrao; Kulisa, Claire Louise; Neuss, Judi Charlotte; Reuberson, James Thomas; US2014/315885; (2014); A1;,
Piperazine – Wikipedia
Piperazines – an overview | ScienceDirect Topics

278788-66-2, (R)-tert-Butyl 3-(hydroxymethyl)piperazine-1-carboxylate is a piperazines compound, ?involved in a variety of chemical synthesis. Rlated chemical reaction is continuously updated

To asolution of 3-(chloroacetyl)-2-methylbenzonitrile (1.7 g, 8.8 mmol) in THF (17.6 mL) was added (R)-4-N-boc-2-hydroxymethyl-piperazine (2.279 g, 10.54 mmol) and DIPEA (3.07 mL, 17.56 mmol) at rt. The reaction mixture wasstirred at rt over the weekend. After concentration, the residue was partitioned between EtOAc and aqueous NaHCO3(saturated). The aqueous layer was extracted with EtOAc (2x). The combined organic phase was washed with brine,dried over anhydrous MgSO4, and filtered. Concentration was followed by purification by prep TLC (silica gel; 10%MeOH/DCM) to give the title compound: LC/MS (M+1)+ = 374.14

278788-66-2, The synthetic route of 278788-66-2 has been constantly updated, and we look forward to future research findings.

Reference：
Patent; Merck Sharp & Dohme Corp.; PASTERNAK, Alexander; BLIZZARD, Timothy; CHOBANIAN, Harry; DE JESUS, Reynalda; DING, Fa-Xiang; DONG, Shuzhi; GUDE, Candido; KIM, Dooseop; TANG, Haifeng; WALSH, Shawn; PIO, Barbara; JIANG, Jinlong; (128 pag.)EP2744499; (2016); B1;,
Piperazine – Wikipedia
Piperazines – an overview | ScienceDirect Topics

With the rapid development and complex challenges of chemical substances, new drug synthesis pathways are usually the most effective.278788-66-2,(R)-tert-Butyl 3-(hydroxymethyl)piperazine-1-carboxylate,as a common compound, the synthetic route is as follows.

A Pyrex yessel was charged with magnetic stirring bar. (2.0 g. 11.42 mmol) of 2-methoxy-4-(oxiran-2-yl) benzonitrile, (3.70 g, 17.12 mmol) of tert-butyl (3R)-3-(hydroxymethyl)piperazine- 1 -carboxylate, and 6 m of EtOH. Then it was introduced in the microwaye reactor and irradiated at 150 C for 3 h. The mixture was cooled to room temperature and the solyent was eyaporated and the resulting residue was purified by column chromatography (silica gel, 1- 20% dichloromethane/MeOH) which afforded the product as a mixture of twodiastereomers (1:1) LCIMS: (IE, miz) [(M + 1) – t-Bu]± = 336.41

278788-66-2, As the paragraph descriping shows that 278788-66-2 is playing an increasingly important role.

Reference：
Patent; MERCK SHARP & DOHME CORP.; PASTERNAK, Alexander; DE JESUS, Reynalda, Keh; DING, Fa-xiang; DONG, Shuzhi; FRIE, Jessica; GU, Xin; JIANG, Jinlong; SHAHRIPOUR, Aurash; PIO, Barbara; TANG, Haifeng; WALSH, Shawn; WO2014/126944; (2014); A2;,
Piperazine – Wikipedia
Piperazines – an overview | ScienceDirect Topics