Methanesulfonic Acid → (2S,3R,4S,5S,6R)-2-[4-chloro-3-[[4-(trifluoromethoxy)phenyl]methyl]phenyl]-6-(hydroxymethyl)-2-methoxy-tetrahydropyran-3,4,5-triol

Temperature

-78 °C

4-bromo-1-chloro-2-[[4-(trifluoromethoxy)phenyl]methyl]benzene 6h (2.33 g, 6.38 mmol) was dissolved in 40 mL of mixed solution (THF and n-hexane, v:v=1:3) and cooled to −78° C., followed by dropwise addition of a solution of nBuLi in n-hexane (3.83 mL, 9.57 mmol). After stirring for 1.5 hours at −78° C., a solution (30 mL) of (3R,4S,5R,6R)-3,4,5-tris(trimethylsilyloxy)-6-(trimethylsilyloxymethyl)tetrahydropyran-2-one 2f (4.47 g, 9.57 mmol) in mixed solution (THF and n-hexane, v:v=1:3) was dropwise added before the reaction mixture was stirred for 2 hours at −78° C. A solution (32 mL) of 0.6 M methanesulfonic acid in methanol was added before the reaction mixture was warmed and stirred for 16 hours at room temperature. Thereafter, the reaction mixture was partitioned after 150 mL of saturated sodium carbonate solution were added. The aqueous phase was extracted with ethyl acetate (100 mL×3) and the organic extracts were combined, dried over anhydrous magnesium sulfate, and filtered. The filtrate was concentrated under reduced pressure. The resulting residue was purified by silica gel chromatography with elution system A to obtain the title compound (2S,3R,4S,5S,6R)-2-[4-chloro-3-[[4-(trifluoromethoxy)phenyl]methyl]phenyl]-6-(hydroxymethyl)-2-methoxy-tetrahydropyran-3,4,5-triol 61 (1.38 g, white solid), yield: 45.2%. 1H NMR (400 MHz, CD3OD): δ 7.61 (d, 1H), 7.51 (dd, 1H), 7.40 (d, 1H), 7.31-7.29 (m, 2H), 7.17 (d, 2H), 4.23-4.12 (m, 2H), 3.94 (d, 1H), 3.86-3.75 (m, 2H), 3.95-3.59 (m, 2H), 3.47-3.42 (m, 1H), 3.10 (s, 3H).

1. stirringwas stirred for 2 hours at −78° C
2. temperaturewas warmed
3. stirringstirred for 16 hours at room temperature
4. customThereafter, the reaction mixture was partitioned after 150 mL of saturated sodium carbonate solution
5. additionwere added
6. extractionThe aqueous phase was extracted with ethyl acetate (100 mL×3)
7. dry with materialdried over anhydrous magnesium sulfate
8. filtrationfiltered
9. concentrationThe filtrate was concentrated under reduced pressure
10. customThe resulting residue was purified by silica gel chromatography with elution system

ORD record

ord-c1a0e02faf1040e0a0f2abd33f8bd01a

Source dataset

uspto-grants-2013_12

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US08609622B2