(4S,5R)-5-[3,5-bis(triflu...;(4S,5R)-5...

TFA (9 L) is added to a 100 L Buchi reactor under an inert atmosphere and is cooled to -5 A solution of (1 /?, 2S)-benzyl-[3, 5-bis(trifluoromethyl)phenyl]-1-hydroxypropan-2-yl carbamate (0.3 g, 0.71 mmol) of step 2-3 in 5 imL of isopropyl alcohol was added with drops of KOH (0.1 g, 1.78 mmol), and then stirred at room temperature for 4 hrs. The reaction was terminateion with water, followed by extraction with ethyl acetate. The organic layer thus formed was dried over anhydrous magnesium sulfate, filtered, and concentrated. The residue was re-crystallized in hexane, and filtered at a reduced pressure to afford the title compound (0.28 g, 90percent). TFA (9L) is added to a 100 L Buchi reactor under an inert atmosphere and is cooled to -5°C. The ketone product from Step 2 (5.50 kg, 13.1 mol) is added as a solid followed by a TFA rinse (2 L). The solution is cooled to -5°C and is stirred until all the solid dissolves. The silane (2.18 kg, 15.7 mol) is added slowly over ~1 h (in two portions) while keeping the temperature at <0°C. The reaction is aged at -2 to -6°C for 15-20 h, at which time LC reveals <2percent of the ketone remains. A 50w/wpercent KOH solution is prepared by adding 13.6kg of KOH pellets (87wpercent) slowly to 10 L water while keeping the highly exothermic dissolution at <30 °C. The solution is stored in a refrigerator.The reaction is quenched with ~2 L of the 50w/wpercent KOH solution with vigorous stirring and cooling, keeping temp at -20 °C. Cold THF (16.5L, previously stored in freezer) is added, followed by slow addition of the remainder of the KOH solution (-13.7 L), followed by a 2 L water rinse while keeping temp <20 °C. After complete addition of KOH, the reaction is aged at room temperature. The reaction is quenched after 3 h with 27.5 L PAC and 20 L 20percentw/v aq NaCl.The aqueous and organic layers are separated. The organic layer is washed with 26 L of 20percentw/v aq NaCl, then with 36 L water, then with 31 L 0.5 N HC1, and finally with 32 L of water. The organic layer is concentrated to -10 L. Heptane (20 L) is added, yielding crystals. The organic layer is concentrated to -10 L. Heptane (20L) is added again, and the organic layer is concentrated to -10 L. Heptane (22 L) is added and the slurry is aged at rt. The solid is filtered and washed with 24 L heptane. A solid product is obtained (98.8percent purity, >99.95percent ee, by LC). The solid is then re-dissolved in 12.5 L MeOH (endothermic). At rt, 3 L water is added, and the mixture is aged to initiate crystallization. Water (9.5 L) is added over ~60min at rt. After aging for 60min, the slurry is filtered and the solid is washed with 5 L MeOH/water (1/1.5), 5 L MeOH/water (1/4) and then 4 L water. The solid product is dried at 50° C under vacuum (99.9percent pure by LC, >99.95percent ee).The (2S) -2-N-Boc-1- (2, 5- difluorophenyl) 60g, 143mmol -1-propanone was dissolved in 120ml of isopropanol, 180ml of toluene, argon, isopropyl alcohol was added aluminum 7.9g, slowly warmed to 50 , stirred overnight. Completion of the reaction, was cooled to 0 deg.] C, the reaction mixture was added to 13.5g, 240mmol potassium hydroxide was slowly warmed to room temperature and stirred for about 1 hour, the reaction was complete. With 1M dilute hydrochloric acid 350ml quench the reaction. Filtered, separated, the organic layer was washed with dilute hydrochloric acid 0.5M200ml, 200ml water, dried over anhydrous sodium sulfate, the solvent was distilled off under reduced pressure, after recrystallization, the compound 26 as a white solid 34.9g, 78percent yield.5.73 g of A was added to a 250 mL four-necked flask, then 32 mL of isopropanol and 48 mL of toluene were added and the mixture was purged with nitrogen at room temperature for 0.5 h. Then add 0.84 g of aluminum isopropoxide while raising the mother liquor to 50 ° C and then stirring the reaction overnight at 50 ° C. The water bath was cooled to 25 ° C and then 1.4 g of potassium hydroxide was added in portions to the mother liquor and the reaction was continued at 25 ° C and the TLC end of the assay. Then, 3 mL of concentrated hydrochloric acid was added dropwise to the mother liquor, then 30 mL of water was added and the crystals were stirred for 1 h at room temperature. The filter cake was washed with 100 mL of purified water and dried under vacuum at 60 ° C and 0.08 MPa for 2 h To give 4.2 g of (4S, 5R) -5- (3, 5-bis (trifluoromethyl) phenyl) -4-methyl-1, 3-oxazolidin-2-one. The crude product obtained above was dissolved in 10 mL of ethyl acetate. Weigh 50 g of 50 to 100 mesh silica gel, 1000 mL of 1: 1 n-hexane and dichloromethane as developing solvent. The target product solution was selected by TLC and concentrated to give 3.65 g of crude product. The crude product is then heated to 80 ° C with 50 mL of n-heptane and, if it is not fully solubilized, add n-heptane until all is dissolved. Hot filter, filter cake at 0 ° C crystallization 2h. (4S, 5R) -5- (3, 5-bis (trifluoromethyl) phenyl) -4- 4-bromo-4- methyl-1, 3-oxazolidin-2-one.

Molecular Weight:313.20
XLogP3:3.4
Hydrogen Bond Donor Count:1
Hydrogen Bond Acceptor Count:8
Rotatable Bond Count:1
Exact Mass:313.05374750
Monoisotopic Mass:313.05374750
Topological Polar Surface Area:38.3
Heavy Atom Count:21
Complexity:386
Defined Atom Stereocenter Count:2
Covalently-Bonded Unit Count:1
Compound Is Canonicalized:Yes