Formaldehyde → HCID 86685104, compound

Temperature

70 °C

Crude (2S,3S,4S,5R,6S)-3,4,5-tribenzyloxy-6-[4-chloro-3-[[4-[2-(cyclopropoxy)ethoxy]phenyl]methyl]phenyl]-6-methoxy-tetrahydropyran-2-carbaldehyde 1e (1.3 g, 1.7 mmol) was dissolved in 15 mL 1,4-dioxane, followed by addition of 37% formaldehyde solution (2.6 mL, 34 mmol) and a solution of sodium hydroxide (204 mg, 5.1 mmol) in 5.1 mL water into the reaction mixture. The reaction mixture was stirred for 4 hours at 70° C., then cooled to 50° C. and stirred for 16 hours. The reaction mixture was extracted with ethyl acetate (20 mL×3) after 20 mL saturated sodium chloride solution were added. The organic extract was washed with saturated sodium bicarbonate solution (20 mL), saturated sodium chloride solution (20 mL), combined, dried over anhydrous magnesium sulfate, and filtered. The filtrate was concentrated under reduced pressure. Then 20 mL of mixed solution (THF and MeOH, v:v=1:1) were added into the residue, before sodium borohydride (130 mg, 3.4 mmol) was added. The reaction mixture was stirred for 30 minutes and concentrated under reduced pressure. The residue was dissolved in ethyl acetate (50 mL) and partitioned. The organic extract was washed with saturated sodium chloride solution (10 mL×2), combined, dried over anhydrous magnesium sulfate, and filtered. The filtrate was concentrated under reduced pressure, then the resulting residue was purified by silica gel chromatography with elution system B to obtain the title compound [(3S,4S,5R,6S)-3,4,5-tribenzyloxy-6-[4-chloro-3-[[4-[2-(cyclopropoxy)ethoxy]phenyl]methyl]phenyl]-2-(hydroxymethyl)-6-methoxy-tetrahydropyran-2-yl]methanol 1f (320 mg, colorless oil), yield: 23.7%.

1. temperaturecooled to 50° C.
2. stirringstirred for 16 hours
3. extractionThe reaction mixture was extracted with ethyl acetate (20 mL×3) after 20 mL saturated sodium chloride solution
4. additionwere added
5. extractionThe organic extract
6. washwas washed with saturated sodium bicarbonate solution (20 mL), saturated sodium chloride solution (20 mL)
7. dry with materialdried over anhydrous magnesium sulfate
8. filtrationfiltered
9. concentrationThe filtrate was concentrated under reduced pressure
10. additionwas added
11. stirringThe reaction mixture was stirred for 30 minutes
12. concentrationconcentrated under reduced pressure
13. dissolutionThe residue was dissolved in ethyl acetate (50 mL)
14. custompartitioned
15. extractionThe organic extract
16. washwas washed with saturated sodium chloride solution (10 mL×2)
17. dry with materialdried over anhydrous magnesium sulfate
18. filtrationfiltered
19. concentrationThe filtrate was concentrated under reduced pressure
20. customthe resulting residue was purified by silica gel chromatography with elution system B

ORD record

ord-353a2caf0ad5424eb08f61959377dc0a

Source dataset

uspto-grants-2013_12

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US08609622B2