With the rapid development and complex challenges of chemical substances, new drug synthesis pathways are usually the most effective.90319-52-1,(R)-4-Phenyloxazolidin-2-one,as a common compound, the synthetic route is as follows.
A reactor was charged with THF (1138 kg) and 2-((ls,4s)-4-(6-fluoroquinolin- 4-yl)cyclohexyl)acetic acid (105.1 kg, 1.0 equiv). The mixture was cooled to -5 to 5 C. Pivaloyl chloride (64.0 kg, 1.45 equiv) was charged. Triethylamine (101.1 kg, 2.70 equiv) was charged, maintaining temperature -5 to 5 C, then the mixture was aged 1 h. (i?)-(-)-4-Phenyl-2- oxazolidinone (68.1 kg, 1.15 equiv) and lithium chloride (20.2 kg, 1.30 equiv) were charged then the reactor wall was rinsed with THF (15.8 kg). The mixture was warmed to 25 C and held for 8 h. Water (1050.6 kg) and isopropyl acetate (825.8 kg) were added into the mixture. After mixing for 1 h, the phases were allowed to separate and the bottom aqueous layer was discarded. The organic stream was then washed with 10 wt% aqueous NaCl (1050 kg). The organic stream was concentrated until 500 L left. Isopropyl acetate (466.3kg) was added, and the organic stream was concentrated until 500 L left. Isopropyl acetate (1850.5 kg) was added into the mixture at 45-55 C and stirred for 1 h. The organic stream was filtered to remove inorganics and the filter was rinsed with isopropyl acetate (187.0 kg). The combined stream was concentrated under reduced pressure until 700 L was left. [00236] The organic stream was heated to 70-75 C until the solid completely dissolved. The mixture was cooled to 45 C then seeds (0.2 kg) were added into the mixture. The mixture was stirred for 1 h. ^-Heptane (1178.5 kg) was added into the mixture over 3 hours, then aged at 45 C for lh. The mixture was cooled to 10 C over 4 hours, and allowed to age for 6 hours. The slurry was filtered with a centrifuge. The solid was rinsed with a pre-mixed solution of isopropyl acetate (45.2 kg) and ^-heptane (321.5 kg). The solids were then rinsed with ft-heptane (2 x 358.2 kg). The cake was dried under vacuum at <50C to obtain 139.6 kg product in 88.2% yield, 99.95 HPLC area percent as a white solid. NMR (600 MHz, DMSO-de) 5 8.80 (d, J = 4.5 Hz, 1H), 8.08 (dd, J = 9.2, 5.8 Hz, 1H), 7.92 (dd, J = 10.9, 2.6 Hz, 1H), 7.63 (td, J = 8.7, 2.6 Hz, 1H), 7.43 (d, J = 4.5 Hz, 1H), 7.39-7.35 (m, 2H), 7.34-7.27 (m, 3H), 5.50 (dd, J = 8.7, 3.8 Hz, 1H), 4.75 (t, J = 8.7 Hz, 1H), 4.16 (dd, J= 8.7, 3.8 Hz, 1H), 3.34-3.25 (m, 1H), 3.17 (dd, J = 15.6, 6.8 Hz, 1H), 3.02 (dd, J = 15.7, 8.0 Hz, 1H), 2.35 (br s, 1H), 1.83-1.75 (m, 2H), 1.73-1.56 (m, 6H); 13C NMR (150 MHz, DMSO-de) d 171.6, 160.7, 159.1, 153.7, 152.2, 152.1, 149.8, 145.1, 140.0, 132.6, 132.6, 128.7, 127.9, 127.1, 127.1, 125.7, 119.0, 118.8, 118.4, 107.1, 107.0, 69.9, 57.0, 37.4, 36.5, 29.6, 29.0, 28.7, 27.4. HRMS (ESI) calculated for C26H26FN2O3 [M + H]+: 433.1922, found 433.1936., 90319-52-1
As the paragraph descriping shows that 90319-52-1 is playing an increasingly important role.
Reference£º
Patent; BRISTOL-MYERS SQUIBB COMPANY; DELMONTE, Albert, J.; COHEN, Benjamin, M.; FRAUNHOFFER, Kenneth, Joseph; KOLOTUCHIN, Sergei; GONZALEZ-BOBES, Francisco; BEUTNER, Gregory, Louis; FREITAG, Adam, Joseph; BULTMAN, Michael, Scott; FAN, Yu; MAITY, Prantik; YOUNG, Ian, Scott; BECK, Hilary, Plake; OSPOV, Maksim; POWERS, Jay, Patrick; REILLY, Maureen, Kay; SHUNATONA, Hunter, Paul; WALKER, James, Ross; ZIBINSKY, Mikhail; (75 pag.)WO2019/6292; (2019); A1;,
Oxazolidine – Wikipedia
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