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.

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 (i?)-4-N-Boc-2-hydroxymethyl-piperazine (149 g, 688 mmol) in THF (3500 mL) and the mixture was stirred at room temperature for 18 h. The reaction was diluted with 3 L EtOAc, washed 2x with 1500 mL 10%> w/w NaHC03 aqueous solution, dried over MgS04, 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.; PIO, Barbara; PASTERNAK, Alexander; SHAHRIPOUR, Aurash; TANG, Haifeng; WALSH, Shawn; WO2013/90271; (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.

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 (i?)-4-N-Boc-2-hydroxymethyl-piperazine (149 g, 688 mmol) in THF (3500 mL) and the mixture was stirred at room temperature for 18 h. The reaction was diluted with 3 L EtOAc, washed 2x with 1500 mL 10%> w/w NaHC03 aqueous solution, dried over MgS04, 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.; PIO, Barbara; PASTERNAK, Alexander; SHAHRIPOUR, Aurash; TANG, Haifeng; WALSH, Shawn; WO2013/90271; (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 (lambda)-3-hydroxymethyl-piperazine-l-carboxylic acid tert-butyl ester (795 mg, 3.68 mmol) in DCM (20 mL) was added triethylamine (1.53 mL, 11.04 mmol). The resulting mixture was cooled to 0 C before the dropwise addition of chloroacetyl chloride (325 muL, 4.05 mmol). The mixture was warmed to RT and stirred for 5 h. The reaction mixture was partitioned between a saturated aqueous solution OfNaHCO3 and DCM. The organic layer was separated and the aqueous layer extracted with DCM. The combined organic fractions were dried (Na2SO4) and concentrated in vacuo. The resulting residue was purified by column chromatography to give the title compound as a colourless oil which was a mixture of rotamers (710 mg, 66%).1H NMR (400 MHz, CDCl3): delta 1.48 (s, 9H), 2.80-2.92 (m, IH), 2.95-3.10 (m, 2H), 3.34-3.44 (m, 1AH), 3.60-3.74 (m, 21Z2H), 3.96-4.16 (m, 31AH), 4.22-4.30 (m, V2Yi), 4.32-4.40 (m, VJS) and 4.63 (bs, V2H)., 278788-66-2

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

Reference：
Patent; F. HOFFMANN-LA ROCHE AG; WO2009/53715; (2009); 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

R)-l-Boc-3-(Hydroxymethyl)piperazine (10 g, 46.2 mmol) was dissolved in a mixture of DCM (180 ml) and sat. NaHC03 (180 ml). CBZ-C1 (6.60 ml, 46.2 mmol) was dissolved in DCM (15 ml) and added dropwise with vigorous stirring. The mixture was stirred for 2.5 hours. The layers were separated and the aqueous phase was extracted with DCM. The combined organic phases were washed with brine, dried over Na2S04 and the solvent was removed in vacuo to give an oil which was used in the next step without 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.; MSD R&D (CHINA) CO. LTD.; WILLIAMS, Peter, D.; MCCAULEY, John, A.; BENNETT, David, J.; BUNGARD, Christopher, J.; CHANG, Lehua; CHU, Xin-Jie; DWYER, Michael, P.; HOLLOWAY, M. Katherine; KEERTIKAR, Kartik, M.; LOUGHRAN, H. Marie; MANIKOWSKI, Jesse, J.; MORRIELLO, Gregori, J.; SHEN, Dong-Ming; SHERER, Edward, C.; SCHULZ, Jurgen; WADDELL, Sherman Tim; WISCOUNT, Catherine, M.; ZORN, Nicolas; SATYANARAYANA, Tummanapalli; VIJAYASARADHI, Sivalenka; HU, Bin; JI, Tao; ZHONG, Bin; WO2015/17393; (2015); 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.

278788-66-2, To Intermediate I 3 (3.99 g, 21.7 mmol) was added tert-butyl (3i?)-3-(hydroxy- methyl)piperazine-l -carboxylate (5.21 g, 24 mmol), and the mixture was suspended in 1,4-dioxane (100 mL). To this was added DIPEA (4.6 mL, 26 mmol) and the mixture was heated at 80C for 1 h. Further DIPEA (9 mL) was added and the mixture was heated at 100C for 48 h. The reaction mixture was cooled to r.t. and concentrated in vacuo, to yield an orange solid which was triturated with water/ether/dichloromethane and filtered. The solid was discarded, and the filtrate was concentrated in vacuo. The resulting orange oil was purified by flash column chromatography on silica [Biotage SNAP 200g, Isolera, gradient elution (80% EtOAc/isohexanes to 100% EtOAc; followed by 100% DCM to 20% MeOH/DCM)], to yield the title compound (4.51 g, 57.1%) as a yellow oil. LCMS (ES+) 364.8 [M+H]+, RT 1.20 minutes (method 3).

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; UCB PHARMA S.A.; KATHOLIEKE UNIVERSITEIT LEUVEN, K.U.LEUVEN R&D; FORD, Daniel James; FRANKLIN, Richard Jeremy; GHAWALKAR, Anant Ramrao; HORSLEY, Helen Tracey; HUANG, Qiuya; REUBERSON, James Thomas; VANDERHOYDONCK, Bart; WO2014/96423; (2014); 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.

DIPEA (84 ml, 480.94 mmol) was added to 53 7-bromo-4,6-dichloro-3-nitroquinoline (60 g, 186.37 mmol) and 55 tert-butyl (R)-3-(hydroxymethyl)piperazine-1-carboxylate (89 g, 410.02 mmol) in 131 i-PrOH (600 ml). The resulting mixture was stirred at 80 C. for 2 hours. The solvent was removed under reduced pressure. The crude product was purified by flash silica chromatography, elution gradient 0 to 20% 57 EtOAc in 148 petroleum ether. Pure fractions were evaporated to dryness to afford 199 tert-butyl (3R)-4-(6-bromo-7-chloro-3-nitroquinolin-4-yl)-3-(hydroxymethyl)piperazine-1-carboxylate (54 g, 58%) as a yellow solid. 1H NMR (DMSO, 300 MHz) 1.16 (1H, t), 1.31-1.46 (9H, m), 1.97 (1H, s), 2.10-2.27 (1H, m), 2.36 (1H, d), 2.66 (1H, s), 3.47 (1H, s), 3.77 (1H, s), 4.01 (1H, q), 4.14 (1H, s), 7.50-7.64 (1H, m), 8.52 (1H, d), 8.62 (1H, s), 11.16 (1H, s). m/z (ES+), [M+H]+=503., 278788-66-2

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

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

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 a solution of imidazole (15.7 g, 231 mmol) in DCM (100 mL) was added SOCh (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-l-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 NH4CI (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 Na2S04, filtered and concentrated under vacuum to give tert-butyl (3aR)-l-oxo-3a,4,6,7-tetrahydro-3H-oxathiazolo[3,4-a]pyrazine-5-carboxylate (5.8 g, 22.1 mmol, 95.6% yield) as a brown 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; MIRATI THERAPEUTICS, INC.; ARRAY BIOPHARMA, INC.; FISCHER, John, P.; FELL, Jay, Bradford; BLAKE, James, F.; HINKLIN, Ronald, Jay; MEJIA, Macedonio, J.; HICKEN, Erik, James; CHICARELLI, Mark, Joseph; GAUDINO, John, J.; VIGERS, Guy, P.A.; BURGESS, Laurence, E.; MARX, Matthew, Arnold; CHRISTENSEN, James, Gail; LEE, Matthew, Randolf; SAVECHENKOV, Pavel; ZECCA, Henry, J.; (529 pag.)WO2017/201161; (2017); 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 a solution of imidazole (15.7 g, 231 mmol) in DCM (100 mL) was added SOCh (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-l-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 NH4CI (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 Na2S04, filtered and concentrated under vacuum to give tert-butyl (3aR)-l-oxo-3a,4,6,7-tetrahydro-3H-oxathiazolo[3,4-a]pyrazine-5-carboxylate (5.8 g, 22.1 mmol, 95.6% yield) as a brown 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; MIRATI THERAPEUTICS, INC.; ARRAY BIOPHARMA, INC.; FISCHER, John, P.; FELL, Jay, Bradford; BLAKE, James, F.; HINKLIN, Ronald, Jay; MEJIA, Macedonio, J.; HICKEN, Erik, James; CHICARELLI, Mark, Joseph; GAUDINO, John, J.; VIGERS, Guy, P.A.; BURGESS, Laurence, E.; MARX, Matthew, Arnold; CHRISTENSEN, James, Gail; LEE, Matthew, Randolf; SAVECHENKOV, Pavel; ZECCA, Henry, J.; (529 pag.)WO2017/201161; (2017); 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

Tert-butyl (R)-3-(hydroxymethyl)piperazine-1-carboxylate (1.68 g, 7.77 mmol) was added to 113 7-bromo-4,6-dichloro-8-fluoro-3-nitroquinoline (1.2 g, 3.53 mmol), and 56 DIPEA (1.571 ml, 8.83 mmol) in NMP (10 ml) under nitrogen, and the resulting solution was stirred at room temperature for 3 hours. The mixture was partitioned between ethyl acetate and water then the organic layer was washed with water (×2) then brine, dried and evaporated then purified by flash silica chromatography, elution gradient 10 to 40% 57 EtOAc in 58 heptane. Pure fractions were evaporated to dryness to afford 115 tert-butyl (R)-4-(7-bromo-6-chloro-8-fluoro-3-nitroquinolin-4-yl)-3-(hydroxymethyl)piperazine-1-carboxylate (0.96 g, 52%) as a yellow solid. m/z: ES+ [M+H]+ 521., 278788-66-2

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

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

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

PREPARATIVE EXAMPLE 9; STEP B; (Bhattacharyya, S. Tetrahedron Lett. 1994,35, 2401.) [] A mixture of the title compound from Step A (1.09 g, 5.04 mmol, 1.0 eq.), paraformaldehyde (300 mg, ? 10.08 mmol, 2.0 eq.), and titanium isopropoxide (1.5 ml, 5.04 mmol, 1.0 eq.) in absolute ethanol (5 ml) was stirred at 70 C for 30 minutes and at room temperature for another 30 minutes. Sodium borohydride (195 mg, 5.04 mmol, 1.0 eq.) was added to the colorless solution. The solution was stirred at room temperature for 12h and at 60 C for another 3h. The solution was cooled to 0 C and treated with a 2.0M aqueous ammonia solution (25 ml, 50.00 mmol, excess) to give a snow-white suspension. The suspension was filtered through a Celite 521 plug and the filtrate was extracted with diethyl ether (4 x 25 ml). The ethereal extracts were combined and washed with brine (10 ml), dried over Na2SO4, filtered, and concentrated under house vacuum at 30 C. The residue was flash chromatographed (CH2Cl2 : 10% NH4OH/MeOH = 9:1 v/v) over silica gel to give the title compound (1.10 g, 95%) as a light-yellow, viscous oil. MS (EI): m/z 231 ([M+H]+, 59%), 175(B+). HR-MS(FAB):Calculated for C11H22N2O3 ([M+H]+): 231.1709. Found: 231.1716.

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

Reference：
Patent; SCHERING CORPORATION; EP1140904; (2005); B1;,
Piperazine – Wikipedia
Piperazines – an overview | ScienceDirect Topics