Category: 278788-66-2

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

A mixture of (R)-tert-butyl-3-(hydroxymethyl)piperazine-1-carboxylate (1 g, 4.62 mmol) and imidazole (0.629 g, 9.24 mmol) was dissolved in CH2Cl2 (10 mL). Tert-butylchlorodiphenylsilane (1.18 mL, 5.08 mmol) was added dropwise over 10 minutes. Upon completion of addition, the mixture was stirred at RT for 3 hours. The reaction mixture was diluted with 50 mL of CH2Cl2 and washed with saturated aqueous sodium bicarbonate (3×20 mL), brine (2×20 mL), dried over magnesium sulfate, and concentrated. Purification via silica gel chromatography using 2-10% methanol in CH2Cl2 gave (R)-tert-butyl-3-(O-tert-butyldiphenylsilane)methyl-piperazine-1-carboxylate as a white solid (1.7 g, 81%). 1H NMR (400 MHz, DMSO-d6) delta 7.63-7.61 (m, 5H), 7.48-7.45 (m, 5H), 4.13-3.44 (m, 5H), 2.80 (d, J=11.8 Hz, 2H), 2.66 (d, J=5.7 Hz, 2H), 1.40 (s, 9H), 1.01 (s, 9H). LC/MS (10%-99% CH3CN (0.035% TFA)/H2O (0.05% TFA)), m/z: M+1 obs=455.5; tR=3.05 min.

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

Reference：
Patent; Martinborough, Esther; Fanning, Lev T.D.; Sheth, Urvi; Wilson, Dean; Termin, Andreas; Neubert, Timothy; Zimmermann, Nicole; Knoll, Tara; Whitney, Tara; Kawatkar, Arati; Lehsten, Danielle; Stamos, Dean; Zhou, Jinglan; Arumugam, Vijayalaksmi; Gutierrez, Corey; US2008/27067; (2008); 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.

Step D: (3S,9aR}-3-(3-Cyano-4-fluoro-2-methyl-phenyl)-3-hydroxy-hexahydro-pyrazino[2,1-c][1,4]oxazine-8-carboxylic acid tert-butyl ester: Diisopropylethylarnine (44.0 mL, 252 mmol)was added to a stirred, room temperature mixture of72 wt% 3-(2-Bromo-acetyl)-6-fluoro-2-methyl-benzonitrile (69 g, 194 mmol) and (R)-4-N-Boc-2-hydroxymethyl-piperazine ( 42.0 g, 194 mmol) in THF (1000 mL) and the mixture was stirred at room temperature for 18h. The reactionwas diluted with 1 L EtOAc, washed 2x with 500 mL 10% w/wNaHC03 aqueous solution,dried over MgS04, filtered and concentrated. The residue was purified by column chromatographyon silica gel ( 40-80% EtOAc/Hexanes, linear gradient), to give the title compound.?~+%, 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; WO2013/28474; (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.

Step D: (3R)-tert-butyl4-(2-(2-chloro:-3-cyano-4-fluorophenyl)-2-hydroxyethyl)-3-(hydroxymethyl)piperazine-1-carboxylate; 2-Chloro-6-fluoro-3-( oxiran-2-yl)benzonitrile (9.1 g,46 mmol) and (R)-tert-butyl3-(hydroxymethyl)piperazine-1-carboxylate (14.9 g, 69.1 mmol)were dissolved in ethanol (1 05 mL) and dispensed into 9 sealed tubes then microwaved at140C for 1 h. The combined reaction mixture was concentrated and purified through a 330gISCO Redi-sep column with 50%-100 ethyl acetate/hexane solvent system to yield the title compound., 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; 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

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 a solution of tert-butyl (3R)-3-(hydroxymethyl)piperazine-1-carboxylate (80.0 g, 370 mmol, 1.0 eq) in Ethyl acetate (1400 mL) was added NaHCO 3 (93.2 g, 1.11 mol, 43.2 mL, 3.0 eq), H 2O (700 mL) and benzyl carbonochloridate (82.0 g, 481 mmol, 68.4 mL, 1.30 eq). The mixture was stirred at 25° C. for 12 hour. After completion, the organic phase was separated, washed with water (500 mL 2) dried over Na 2SO 4 and filtered. The solvent was removed under vacuum to give a residue. The residue was purified by column chromatography (SiO 2, Petroleum ether/Ethyl acetate=40/1 to 1/1). The product 1-benzyl 4-tert-butyl (2R)-2-(hydroxymethyl)piperazine-1,4-dicarboxylate (85.0 g, 235 mmol, 64% yield, 96% purity) was obtained as a yellow oil. LCMS [ESI, M-99]: 251.

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

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 (384 mg, 1.78 mmol) was added to a mixture of 53 7-bromo-4,6-dichloro-3-nitroquinoline (260 mg, 0.81 mmol) and 56 DIPEA (0.316 ml, 1.78 mmol) in NMP (4 ml). The mixture was heated at 75 C. for 2 hours, then allowed to cool to room temperature. The mixture was partitioned between ethyl acetate (100 ml) and water (100 ml). The aqueous layer was extracted with ethyl acetate (100 ml) and the extracts combined with the organic layer. The combined organics were washed sequentially with water (2×100 ml) and saturated brine (50 ml), then dried and evaporated to dryness to give a brown gum. The crude product was purified by flash silica chromatography, elution gradient 20 to 40% 57 EtOAc in 58 heptane. Pure fractions were evaporated to dryness to afford 59 tert-butyl (R)-4-(7-bromo-6-chloro-3-nitroquinolin-4-yl)-3-(hydroxymethyl)piperazine-1-carboxylate (218 mg, 54%) as a yellow solid. 1H NMR (500 MHz, DMSO, 27 C.) 1.43 (9H, s), 3.34-3.53 (5H, m), 3.64 (3H, d), 4.34-4.42 (1H, m), 4.58 (1H, t), 8.38 (1H, d), 8.49 (1H, s), 9.05 (1H, s). m/z: ES+ [M+H]+ 501.

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

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

2-chloro-6-fluoro-3-(oxiran-2-yl)benzonitrile (9.1 g, 46 mmol) and (R)-tert-butyl 3-(hydroxymethyl)piperazine-1-carboxylate (14.9 g, 69.1 mmol) were dissolved in ethanol (105 mL) and dispensed into 9 sealed tubes thenmicrowaved at 140C for 1 h. The combined reaction mixture was concentrated and purified through a 330g ISCORedi-sep column with 50%-100 ethyl acetate/hexane solvent system to yield 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; 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

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 A:(3R)-tert-butyl 4-(2-(3-cyano-2,4-difluorophenyl):-2-hydroxyethyl)-3-(hydroxYmethyl)piperazine-1-carboxylateate; 2,6-difluoro-3-( oxiran-2-yl)benzonitrile (3. 70 g, 20.4mmol) and (R)-tert-butyl3-(hydroxymethyl)piperazine-1-carboxylate (6.63 g, 30.6 mmol) weredissolved in ethanol (36.0 mL) then placed in 3-20mL sealed tubes and microwaved at 140C for 1 h. The solvents were evaporated and the combined residue was purified by chromatographythrough a 120g ISCO Redi-sep column with 50% to 100% ethyl acetate/hexane solvent system toyield the title compound LC-MS (IE, m/z): 398 [M +1]+., 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

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.

Preparation of (R)-tert-b ty 3-(hydroxymethyl)-4-methylpiperazine-l-carboxylateTo a solution of (R)-tert-b ty 3-(hydroxymethyl)piperazine-l-carboxylate (115 mg, 0.53 mmol) in acetonitrile (1.4 mL) and water (0.3 mL) was added Formalin (0.11 mL, 1.6 mmol) followed by sodium triacetoxyborohydride (225 mg, 1.1 mmol). The reaction mixture was stirred for 20 minutes at ambient temperature. The reaction mixture was then basified via the addition of saturated aqueous sodium carbonate solution (1 mL), diluted with methylene chloride (50 mL) and methanol (5 mL), and washed with saturated aqueous sodium bicarbonate solution (2 X 15 mL). The organic layer was separated, dried over sodium sulfate, and concentrated in vacuo to afford a white crystalline solid, which was used in the next step without any further purification (120 mg, 98%)., 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£º
Patent; F. HOFFMANN-LA ROCHE AG; DYKE, Hazel Joan; GAZZARD, Lewis J.; WILLIAMS, Karen; WO2011/73263; (2011); 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.

A solution of NaOEt was prepared from NaH (60% dispersion in mineral oil) (0.723 g, 19 mmol) and 20 mL EtOH. To this solution was added diethyl carbonate (8.50 mL, 70 mmol) and the mixture was transferred to a solution of (R)-4-N-BOC-2-hydroxymethyl-piperazine (1.523 g, 7.0 mmol) in 80 mL of EtOH and heated at 78 C. After 6.5 h the reaction was cooled to RT and filtered. The filtrate was concentrated to dryness to give an off-white amorphous solid.

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

Reference£º
Patent; Amgen Inc.; US2006/199817; (2006); 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.

1-fluoro-4-nitrobenzene (1.056 g, 7.49 mmol) and potassium carbonate (3.10 g, 22.5 mmol) were suspended in anhydrous DMF (10 mL) . (R)-tert-butyl 3- (hydroxymethyl)piperazine-1-carboxylate (1.70 g, 7.86 mmol) was added and the mixture was heated at 90 C for21 h. After cooling the mixture was partitioned between brine/water (100 mL) and ethyl acetate (25 mL) . The aqueous layer was separated and further extracted with ethyl acetate (3 x 25 mL) . The combined ethyl acetate fractions were washed with brine/water (1:1, 4 x 25 mL),dried (Na2504), filtered and reduced in vacuo. The resulting residue was purified by silica gel chromatography (gradient 20-100% ethyl acetate in cyclohexane) to afford the title compound (0.69 g, 27.3LCMS (Method C) : = 1.38 mi m/z = 338 [M+H]., 278788-66-2

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

Reference£º
Patent; ALMAC DISCOVERY LIMITED; HARRISON, Timothy; TREVITT, Graham; HEWITT, Peter Robin; O’DOWD, Colin Roderick; BURKAMP, Frank; WILKINSON, Andrew John; SHEPHERD, Steven D.; MIEL, Hugues; WO2015/92431; (2015); A1;,
Piperazine – Wikipedia
Piperazines – an overview | ScienceDirect Topics