TF-HF

7.5 g of Taf2 and 70 g of methanol are mixed in a reaction flask, then 1.5 g of potassium carbonate is added into the reaction flask and stirred at room temperature for 1.5 hours. After the reaction, acetic acid is added for neutralization. The reaction solution is extracted by ethyl acetate and water after concentration. The organic layer is dried and concentrated and then purified by silica gel column chromatography (EA/Hexane=1/1.5), and (1S, 5R, 6R, 7R)-2-oxa-7-hydroxy-6- [(1E)-3 , 3 -difluoro-4-phenoxy-1 -buten yl]bicyclo[3, 3, 0]octan-3-one (Taf3) is obtained.5.5 g of Taf3 and 50 g of tetrahydrofuran is added to the reaction flask, then the temperature is dropped to -70 C. 30 g of diisobutylaluminum hydride (20% dissolved in hexane) is added into the reaction flask and stirred at -70 C. for 30 minutes. After reaction, water is gradually added for neutralization. Then, the reaction solution is added to aqueous solution of saturated potassium sodium tartrate and stirred for 1 hour. The aqueous layer is extracted by ethyl acetate, and after combining with the organic layer, it is extracted by saturated saline. After removing water and concentration of the organic layer, 5.7 g of (1 S , 5R, 6R, 7R)-2-oxa-3, 7-dihydroxy-6- [(1E)-3, 3-difluoro-4-phenoxy-1-b utenyl]bicyclo[3, 3, 0]octane (Taf4) is obtained.Stirring was started and 350 ml of methanol (10X) was added to the kettle; the temperature was controlled at 20±5C.The prepared compound of formula 4 (35 g, 1.0 eq) was added to the reaction kettle at a time; potassium carbonate (5.75 g, 0.6 eq) was added to the reaction vessel;Degree of control at 20 ± 5 C, stirring 2h; temperature control at 0 ± 5 C, slowly add 2.4 volume of 1N hydrochloric acid solution, adjust the pH toAcidity, stirring for 1h; filtration, washing the filter cake with 70 ml of mixed solvent (MeOH/H2O=4/1, v/v, 2X); the filtrate was spin-dried and dissolved in water105 mL DCM (3X); 105 mL water (3X) extraction; aqueous phase extracted with 105 mL DCM (3X); organic phase combined; organicThe phase was washed with 105 ml (3X) saline, and the organic phase was dried over anhydrous sodium sulfate; after the organic phase was concentrated under reduced pressure, n-heptane (20X) was added.A white solid was crystallized and filtered to obtain 22.5 g of the product in 80% yield. HPLC: 99%. 1 H NMR(CDCl3): delta 2.0-2.8(m, 6H), 4.09(m, 1H), 4.20(t, J=11.5 Hz, 2H), 4.94(m, 1H), 5.84(dt, J=15.6, 11.2 Hz, 1H), 6.07 (m, 1H), 6.91(d, J=7.8 Hz, 2H), 7.02(t, J=7.3 Hz, 1H), 7.31(m, 2H). 19 F NMR(CDCl3): -103.6(m).

2H-cyclopentano[B]furan-2-one, 4-[(1E)-3,3-difluoro-4-phenoxy-1-buten-1-yl]hexahydro-5-hydroxy-,(3AR,4R,5R,6AS)-(...), i.e. (3aR,4R,5R,6aS)-4-((E)-3,3-difluoro-4-phenoxybutyl-1-en-1-yl)-5-hydroxyhexahydro-2H-cyclopentane[b]furan-2-one, belongs to the intermediates of tafluprost.

Molecular Weight:324.32
XLogP3:2.5
Hydrogen Bond Donor Count:1
Hydrogen Bond Acceptor Count:6
Rotatable Bond Count:5
Exact Mass:324.11731538
Monoisotopic Mass:324.11731538
Topological Polar Surface Area:55.8
Heavy Atom Count:23
Complexity:460
Defined Atom Stereocenter Count:4
Defined Bond Stereocenter Count:1
Covalently-Bonded Unit Count:1
Compound Is Canonicalized:Yes