ChemicalBook CAS DataBase List Empagliflozin

Empagliflozin synthesis

3synthesis methods

Product Name:Empagliflozin
CAS Number:864070-44-0
Molecular formula:C23H27ClO7
Molecular Weight:450.91

Commercial 5-iodo-2-chlorobenzoic acid (97) was first converted to the corresponding acid chloride, prior to subjection to commercially available fluorobenzene (98) under Friedel–Crafts conditions to generate the desired fluorobenzophenone 99 in 94% yield after isolation by recrystallization from aqueous isopropanol. The fluorobenzophenone (99) was then reacted with commercially available (S)-3-hydroxytetrahydrofuran (100) and potassium tertbutoxide in THF to afford ethereal benzophenone 101. Next, removal of the ketone functionality within 101 was achieved through the use of 1,1,3,3-tetramethyldisiloxane (TMDS) in the presence of aluminum chloride in toluene to deliver diaryl iodide 102. This iodide was subsequently converted to the corresponding Grignard reagent and subjected to gluconolactone 103, giving rise to an intermediate lactol which was then sequentially treated with aqueous citric acid, methanolic HCl, and triethylsilyl hydride and aluminum trichloride to ultimately furnish empagliflozin (XIII) in 73% yield across the four-step protocol.

1279691-36-9 Synthesis

(2S,3R,4S,5S,6R)-2-(3-(4-((S)-tetrahydrofuran-3-yloxy)benzyl)-4-chlorophenyl)-tetrahydro-6-(hydroxyMethyl)-2-Methoxy-2H-pyran-3,4,5-triol

1279691-36-9
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864070-44-0
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Yield:864070-44-0 82.5%

Reaction Conditions:

with triethylsilane;Aluminum Chloride in dichloromethane;acetonitrile;

Steps:

3 (2S,3R,4S,5R,6R)-2-(4-chloro-3- (4-(((S) -tetrahydrofuran-3-yl)oxy)benzyl)phenyl)-6- (hydroxymethyl) tetrahydro-2H-pyran-3,4,5-triol

Add acetonitrile: dichloromethane (1: 1,200mL by volume) to a 1L dry reaction flask.Stir down to 0 10 , then add 42g in orderAluminum trichloride and 32.5gTriethylsilane,The reaction was stirred for 30 min.50g(2S, 3R, 4S, 5R, 6R) -2- (4-chloro-3- (4-(((S) -tetrahydrofuran-3-yl) oxy) benzyl) phenyl) -6- (hydroxymethyl ) 2-methoxytetrahydro-2H-pyran-3,4,5-triol in acetonitrile: dichloromethane(Volume ratio 1: 1, 200 mL) The solution was dropped into the above reaction system, and the dropping was completed in 1 to 2 hours;The temperature was controlled at 20 to 30 ° C and the reaction was stirred for 1 to 2 hours. Add 400mL of water,The organic solvent was distilled off under reduced pressure, and the reaction solution was extracted with 200 mL × 2 ethyl acetate.The organic phases were combined, washed once with saturated brine, and concentrated under reduced pressure to give a pale yellow oil.Purity 90.5%.Add 50 mL of ethyl acetate to the concentrate, turn on the stirring, and lower the temperature to -40 ° C to -50 ° C.After precipitation of a large amount of white solid, stirred for 0.5 h, and 250 mL of n-heptane was added dropwise to the reaction.Stir for 0.5h, filter with suction, and place the filter cake in a hot air circulation drying box for 15h.38.7 g of the title compound was obtained, with a molar yield of 82.5% and a purity of 98.3%.

References:

CN110407891,2019,A Location in patent:Paragraph 0043-0048

864070-37-1 Synthesis

((2R,3S,4R,5R,6S)-6-(4-chloro-3-(4-((S)-tetrahydrofuran-3-yloxy)benzyl)phenyl)-3,4,5-trihydroxytetrahydro-2H-pyran-2-yl)Methyl acetate

864070-37-1
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(R)-3-(p-toluenesulfonyl) oxytetrahydrofuran

219823-47-9
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864070-44-0
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References

D-Glucitol, 1,5-anhydro-1-C-[4-chloro-3-[[4-[[(3S)-tetrahydro-3-furanyl]oxy]phenyl]methyl]phenyl]-

1417573-74-0
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864070-44-0
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References

Empagliflozin Related Search:

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