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.
The chiral intermediate (4S,5R)-5-(3,5-bis(trifluoromethyl)phenyl)-4-methyloxazolidin-2-one (compound 11 in Scheme 3, prepared by procedure of WO 2007/005572) (28.0 g) 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 layerwas 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 Formula IX (anacetrapib) as an amorphous material. The impurity (4S,5R)-5-(3,5-bis(trifluoromethyl)phenyl)-3-((5l-ethyl-4l-fluoro-2′-methoxy-4-(trifluoromethyl) biphenyl-2-yl)methyl)-4-methyloxazolidin-2-one (DMAP) (-3%), which is formed from 2′-(chloromethyl)-5-ethyl-4- fluoro-2-methoxy-4′-(trifluoromethyl)biphenyl (EBFCI) present in the starting material under the conditions described in Step 7, was detected in the product.
As the paragraph descriping shows that 875444-08-9 is playing an increasingly important role.
Reference£º
Patent; LEK PHARMACEUTICALS D.D.; HUMLJAN, Jan; MARAS, Nenad; WO2013/91696; (2013); A1;,
Oxazolidine – Wikipedia
Oxazolidine | C3H7NO – PubChem