Category: 875444-08-9

With the rapid development and complex challenges of chemical substances, new drug synthesis pathways are usually the most effective.875444-08-9,(4S,5R)-5-(3,5-Bis(trifluoromethyl)phenyl)-4-methyloxazolidin-2-one,as a common compound, the synthetic route is as follows.

875444-08-9, Step 7: Synthesis of (4S,5R)-5-[3,5-bis(trifluoromethyl)phenyl]-3-[[2-(4-fluoro-2-methoxy-5-propan-2- ylphenyl)-5-(trifluoromethyl)phenyl]methyl]-4-methyl- 1, 3-oxazolidin-2-one (anacetrapib); The chiral intermediate (4S,5R)-5-(3,5-bis(trifluoromethyl)phenyl)-4-methyloxazolidin-2-one (compound of formula XV; cf. also compound 11 in Scheme 3) (28.0 g) prepared by the procedure of WO 2007/005572 is dissolved in DMF (300 mL) and cooled to -15C. 2 M NaHMDS (39.2 mL, 1 .05 eq) was then added over 1 h, followed by addition of the biaryl chloride 7 (Scheme 3 ) (28.0 g) in DMF (50 mL), maintaining the internal temperature below – 10 C. The mixture was warmed to + 12 C and was aged until complete conversion took place. Then 5M HCI (35 mL) was added, followed by 160 mL of 10% IPAC/Heptanes and 340 mL of water, keeping the temperature between 10C and 20C throughout. The layers were cut and the organic layer was washed twice with 150 mL of 1/1 DMF/water followed by two 140 mL water washes. The organic layer was then removed under reduced pressure and the resulting residue was purified by flash chromatography (EtOAc/hexanes) to remove the excess oxazolidinone 11 (Scheme 3). The obtained colorless oil was then dissolved in refluxing heptanes (200 mL) and the solution was slowly cooled to -20 C. The resulting slurry was then stirred at -20 C for 2 hours and filtered. The filter cake was washed with cold heptanes and was then dried, yielding 44.0 g (88%) of the desired product of compound of formula XV” (anacetrapib) as an amorphous material. An impurity of compound of formula XVII” (4S,5R)-5-(3,5-bis(trifluoromethyl)phenyl)-3-((5,-ethyl-4,-fluoro-2′- methoxy-4-(trifluoromethyl) biphenyl-2-yl)methyl)-4-methyloxazolidin-2-one (DMAP) is present in the thus obtained anacetrapib in an amount of about 3 % by weight relative to the total amount of anacetrapib product. DMAP originates from 2′-(chloromethyl)-5-ethyl-4-fluoro-2-methoxy-4′-(trifluoromethyl)biphenyl (EBFCI) representing an impurity which forms in the preparation path of 2′-(chloromethyl)-4-fluoro-5-isopropyl-2-methoxy- 4′-(trifluoromethyl)biphenyl under the above described conditions.

875444-08-9 (4S,5R)-5-(3,5-Bis(trifluoromethyl)phenyl)-4-methyloxazolidin-2-one 23583229, aoxazolidine compound, is more and more widely used in various fields.

Reference£º
Patent; LEK PHARMACEUTICALS D.D.; HUMLJAN, Jan; MARAS, Nenad; WO2012/85133; (2012); A1;,
Oxazolidine – Wikipedia
Oxazolidine | C3H7NO – PubChem

875444-08-9,875444-08-9, (4S,5R)-5-(3,5-Bis(trifluoromethyl)phenyl)-4-methyloxazolidin-2-one is a oxazolidine compound, ?involved in a variety of chemical synthesis. Rlated chemical reaction is continuously updated

To a solution of (4S,5R)-5-[3,5-bis(trifluoromethyl)phenyl]-4- methyloxazolidin-2-one (46g, 147mol), obtained in step 2, in DMF (150ml) was dropwise added NaHMDS (sodium hexamethyldisilazide) (176 ml, 176 mol) at -40C. The reaction mixture was stirred for 30 min, and slowly added with drops of a dilution of 2-chloro-5- (trifluoromethyl)pyridin-3-yl-methane chloride, obtained in step 1 , in DMF (30ml). The resulting reaction mixture was heated to room temperature, stirred for 3 hrs, diluted with ethyl acetate (200 ml), and added with water (500 ml) to terminate the reaction. The organic layer thus formed was withdrawn, washed with water (2.5 I), and filtered through silica-selite pad at a reduced pressure to afford the title compound (60g, 67%). 1 H NMR (400MHz, CDCI3) . 8.64 (s, 1 H), 8.01 (s, 1 H), 7.90 (s, 1 H), 7.82 (s, 2H), 5.76 (d, J = 8.0Hz, 1 H), 4.84 (d, J = 16.0Hz, 1 H), 4.47 (d, J = 16.4Hz, 1 H), 4.22 (m, 1 H), 083 (d, 3H).

The synthetic route of 875444-08-9 has been constantly updated, and we look forward to future research findings.

Reference£º
Patent; DONG-A ST CO.,LTD; PARK, Jang Hyun; SONG, Seung Hyun; CHUNG, Han Kook; KIM, Heung Jae; LEE, Ji Hye; JANG, Byeong Jun; KIM, Eun Jung; JUNG, Hae Hum; RYU, Chae Lim; HWANG, Jae-Sung; LEE, Hyung Ki; KANG, Kyung Koo; KIM, Soon Hoe; WO2014/157994; (2014); A1;,
Oxazolidine – Wikipedia
Oxazolidine | C3H7NO – PubChem

875444-08-9, (4S,5R)-5-(3,5-Bis(trifluoromethyl)phenyl)-4-methyloxazolidin-2-one is a oxazolidine compound, ?involved in a variety of chemical synthesis. Rlated chemical reaction is continuously updated,875444-08-9

Step 7. (4S,5R)-5-(3,5-bis(trifluoromethyl)phenyI)-3-((4′-fluoro-5,-isopropyl-2*-methoxy-4- (trifluo Oxazolidinone IotaPi (9.58 g, 30.6 mmol), biaryl chloride Pi (10.83 g, 30.0 mmol), tetrabutylammonium iodide (0.02 molar equivalents, based on the amount of biaryl chloride), K2CO3 (2 equivalents), and DMF (12 mL) were charged to a 100 mL flask, and the resulting slurry was stirred at 60 C for 17 hours. Then n-heptane and water were added at the same temperature. The aqueous layer was removed, and the organic layer was washed with water. The product was crystallized by cooling the organic mixture. Isolated crystals were washed with heptane and dried to afford 17.60 g of the titled compound (27.6 mmol, 92 %).

As the paragraph descriping shows that 875444-08-9 is playing an increasingly important role.

Reference£º
Patent; MERCK SHARP & DOHME CORP.; CHUNG, Cheol; HUMPHREY, Guy; MALIGRES, Peter, E.; WRIGHT, Timothy, J.; WO2013/66768; (2013); A1;,
Oxazolidine – Wikipedia
Oxazolidine | C3H7NO – PubChem

875444-08-9,With the rapid development and complex challenges of chemical substances, new drug synthesis pathways are usually the most effective.875444-08-9,(4S,5R)-5-(3,5-Bis(trifluoromethyl)phenyl)-4-methyloxazolidin-2-one,as a common compound, the synthetic route is as follows.

Oxazolidinone 9 (81 mg, 0.257 mmol) was placed in a 5 mL vial, which was purged with nitrogen, and then dissolved in DMF (900 mu, 849.60 mg). The solution was cooled to -20C. NaHMDS (129 mu, 0.257 mmol) was added slowly to maintain the reaction temperature at less than -15C. The mixture was aged for 5 minutes, and then the pyridyl chloride 8 (90 mg, 0.257 mmol) was added as a solution in DMF (900 mu). The reaction was warmed to room temperature slowly. The reaction was complete after 2h at ambient temperature. The reaction was quenched with MTBE and water. The layers were separated. The organic layer was washed with water, then dried with MgSC^, and the solvent was removed by evaporation. Compound 10 (150 mg) was obtained, which could be used directly in the next step.

As the paragraph descriping shows that 875444-08-9 is playing an increasingly important role.

Reference£º
Patent; MERCK SHARP & DOHME CORP.; THOMPSON, Christopher, F.; SWEIS, Ramzi, F.; WO2011/28395; (2011); A1;,
Oxazolidine – Wikipedia
Oxazolidine | C3H7NO – PubChem

With the rapid development and complex challenges of chemical substances, new drug synthesis pathways are usually the most effective.875444-08-9,(4S,5R)-5-(3,5-Bis(trifluoromethyl)phenyl)-4-methyloxazolidin-2-one,as a common compound, the synthetic route is as follows.,875444-08-9

Triaryl oxazolidinone methyl ester; To a IOOL flask was added oxazolidinone 30 (1.35kg) and dry DMF (30.8L). The synthesis of oxazolidinone 30 is provided later. After cooling to -15 to -20 0C, NaHMDS (1.96L of 2M solution) was added, and the mixture was aged 15-30 min. The triaryltosylate 29 (2.2 kg) in DMF was added to the resulting sodium salt of oxazolidinone 30, and the mixture was allowed to warm to 0 to 5 0C. After the triaryl tosylate was consumed, 2.44 L of 5M HCl was added, followed by 22L of 20% heptane/ethyl acetate. Finally, water (11 L) was added slowly. The layers were separated and then the organic layer was washed with DMF:water twice and then with water twice. The organic layer was assayed for yield and then filtered through a plug of silica gel to remove excess oxazolidinone 30. The solution was then solvent switched to methanol and used in the final step.

The synthetic route of 875444-08-9 has been constantly updated, and we look forward to future research findings.

Reference£º
Patent; MERCK & CO., INC.; WO2008/82567; (2008); A1;,
Oxazolidine – Wikipedia
Oxazolidine | C3H7NO – PubChem

With the rapid development and complex challenges of chemical substances, new drug synthesis pathways are usually the most effective.875444-08-9,(4S,5R)-5-(3,5-Bis(trifluoromethyl)phenyl)-4-methyloxazolidin-2-one,as a common compound, the synthetic route is as follows.

875444-08-9, To a solution of (45,5ii)-5-[3,5-bis( fluorome l)phenyl]-4-methyl-l,3- oxazolidin-2-one (254 g, 809 mmol) in THF (4L) was added NaH (60% dispersion in mineral oil) (27 g, 675 mmol). After stirring the reaction at room temperature for 10 minutes, 3-bromo- 2-(hromomethyl)-6-crdoropyridine (154 g, 540 mmol) was added as a solution in THF (500 rnL). The reaction was stirred at room temperature for 1 hours. The reaction was then diluted with EtOAc (8L) and washed with water (2 x 1L) and brine (1L), dried over Na2SC<4, filtered, and concentrated. Purification of the residue by flash chromatography on silica gel with 0 to 40% EtOAc/heptanes afforded (45,5>?)-5-[3,5-bis(trifluoromethyl)phenyI]-3-[(3-bromo-6- chloropyridin-2-yl)m^ LCMS = 518.8 (M+l)+ 1HNMR (CDCI3, 500 MHz) delta 7.90 (s, lH), 7.81-7.83 (m, 3H), 7.18 (d, J= 8.5 Hz, 1H), 5.87 (d, J= 8.5 Hz, 1H), 5.02 (d, J= 17.2 Hz, 1H), 4.42 (m, 1H), 4.32 (d, J= 17.1 Hz, 1H), 0.80 (d, J= 6.6 Hz, 3H).

The synthetic route of 875444-08-9 has been constantly updated, and we look forward to future research findings.

Reference£º
Patent; MERCK SHARP & DOHME CORP.; THOMPSON, Christopher, F.; SWEIS, Ramzi, F.; WO2011/28395; (2011); A1;,
Oxazolidine – Wikipedia
Oxazolidine | C3H7NO – PubChem

With the rapid development and complex challenges of chemical substances, new drug synthesis pathways are usually the most effective.875444-08-9,(4S,5R)-5-(3,5-Bis(trifluoromethyl)phenyl)-4-methyloxazolidin-2-one,as a common compound, the synthetic route is as follows.

875444-08-9, A solution of (45,,5i?)-5-[3,5-bis(trifluoromethyl)phenyl]-4-methyl-l ,3-oxazoIidin-2-one(614 mg, 1.961 mmol) in THF (20 mL) was cooled to 0 C. NaH (58.8 mg, 2.451 mmol) was added. The mixture was stirred at 0 C for 30 min. The title compound from Step E (462 mg, 1.63 mmol) in THF (30 mL) was added. The mixture was stirred at 0 C and then room temperature for 4 h. Saturated NH4CI (10 mL) was added. The mixture was extracted with ethyl acetate (3 x 10 mL). The combined organic fractions were washed with brine (saturated, 10 mL), dried (Na2S04), filtered and the solvent was evaporated under reduced pressure. The residue was purified by column chromatography on silica gel Biotage 40S, eluting with EtOAc/hexane (30/70) to give the title compound as a colorless solid. NMR (CDC13} 500 MHz) delta 7.94 (s, 1H), 7.82 (s, 2H), 5.85 (d, J= 8.5 Hz, 1H), 5.00 (d, J- 17.5 Hz, 1H), 4.46 (m, 1H), 4.31 (d, J = 18.0 Hz, 1H), 2.60 (s, 6H), 0.83 (d, J= 7.0 Hz, 3H).

875444-08-9 (4S,5R)-5-(3,5-Bis(trifluoromethyl)phenyl)-4-methyloxazolidin-2-one 23583229, aoxazolidine compound, is more and more widely used in various fields.

Reference£º
Patent; MERCK SHARP & DOHME CORP.; LU, Zhijian; CHEN, Yi-Heng; SMITH, Cameron; LI, Hong; THOMPSON, Christopher, F.; SWEIS, Ramzi; SINCLAIR, Peter; KALLASHI, Florida; HUNT, Julianne; ADAMSON, Samantha, E.; DONG, Guizhen; ONDEYKA, Debra, L.; QIAN, Xiaoxia; SUN, Wanying; VACHAL, Petr; ZHAO, Kake; WO2012/58187; (2012); A1;,
Oxazolidine – Wikipedia
Oxazolidine | C3H7NO – PubChem