ChemicalBook CAS DataBase List (5R)-3-(3-Fluoro-4-(4-morpholinyl)phenyl)-5-hydroxymethyl-2-oxazolidione

(5R)-3-(3-Fluoro-4-(4-morpholinyl)phenyl)-5-hydroxymethyl-2-oxazolidione synthesis

10synthesis methods

Product Name:(5R)-3-(3-Fluoro-4-(4-morpholinyl)phenyl)-5-hydroxymethyl-2-oxazolidione
CAS Number:168828-82-8
Molecular formula:C14H17FN2O4
Molecular Weight:296.29

60456-26-0

N-BENZYLOXYCARBONYL-3-FLUORO-4-MORPHOLINOANILINE

168828-81-7

(5R)-3-(3-Fluoro-4-(4-morpholinyl)phenyl)-5-hydroxymethyl-2-oxazolidione

168828-82-8

GENERAL STEPS: Example 3: Preparation of (R)-3-[3-fluoro-4-(4-morpholinophenyl)]-5-hydroxymethyl-2-oxazolidinone [131] To a mixed solution of n-butanol (51.5 g) and THF (100 ml) was added slowly at 20-30°C under nitrogen protection n-butyllithium (1.6 M in hexanes, 391.7 g), keeping the reaction temperature at 10-20°C. The process was continued for 45-60 minutes. In another reactor, N-carboxyphenylmethoxy-3-fluoro-4-morpholino aniline (100 g) was dissolved in THF (500 ml) under nitrogen protection and stirred at 20-30 °C. Subsequently, the mixture was cooled to -15 to -5°C, and the n-butyllithium solution prepared as described previously was slowly added, maintaining the temperature at -15 to -5°C for 45-60 minutes of reaction. Then, (R)-(-)-glycidyl butyrate (48.0 g) was slowly added to this solution and kept at -10 to -5°C for 1 hour. After the addition was completed, the reaction temperature was raised to 8-13°C maintained at 8-13°C for 1 hr, and then raised to 13-15°C for 4-5 hrs of reaction. After completion of the reaction, water (800 ml) and ethyl acetate (300 ml) were added for layering. The organic layer was washed with ethyl acetate-hexane mixture and the solid was dried in an air pan drier at 55-60 °C. Yield: 0.765 g in 85% yield. [132]

Carbamic acid, [3-fluoro-4-(4-morpholinyl)phenyl]-, ethyl ester

565176-83-2
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60456-26-0 Synthesis

60456-26-0
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168828-82-8
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Yield: 80%

Reaction Conditions:

Stage #1:N-ethoxycarbonyl-3-fluoro-4-morpholinyl aniline with n-butyllithium in tetrahydrofuran;hexane at -78; for 3.5 h;Inert atmosphere;
Stage #2:(R)-glycidyl butyrate in tetrahydrofuran;hexane at -78 - 20;
Stage #3: with ammonium chloride in tetrahydrofuran;hexane;water at 20; for 0.5 h;Product distribution / selectivity;

Steps:

5.a
Example-S(a): Preparation of (R)-[N-3-(3-fluoro-4-morpholinylphenyl)-2- oxo-5- oxazolidinyljmethanol (VIII) starting from N-carboethoxy-3-fluoro-4- morpholinylanilineN-carboethoxy-3-fluoro-4-morpholinylaniline (100 g) was dissolved in THF (500 ml). To the resulting solution, n-butyllithium (245 ml in hexane) was added under nitrogen at -78°C over 1.5h and stirred for 2h, further a solution of R-(-)-glycidyl butyrate (53.75 g, in THF (100 ml)) was added. The resulting solution was stirred at -78°C for 2h, further it was warmed to room temperature and stirred for overnight. To the resulting thick slurry, saturated ammonium chloride (345 ml) was added followed by the addition of water (300 ml). It was stirred at room temperature for 30 min and was concentrated. Further, water (500 ml) was added and the suspension was again stirred at 50-55°C for lh and then at 25-30°C for next lh. The solid mass was filtered, washed with water and suck dried for lh. The filtrate was extracted with toluene. To the combined toluene layer, the suck dried material obtained above was added and heated to reflux and further concentrated. The concentrated solution was cooled to room temperature and stirred for lh. The solid mass was filtered, washed with toluene and dried to obtain the titled compound (110 g) with 80% yield.

References:

JUBILANT LIFE SCIENCES LIMITED;GUPTA, Ashish, Kumar;SINGH, Shishupal;PANDA, Atulya, Kumar;BISWAS, Sujay;VIR, Dharam WO2011/114210, 2011, A2 Location in patent:Page/Page column 20

496031-56-2 Synthesis