Reaction #87484

Reaction equation

trityl chloride

benzyl chloride

D-glucose

trifluoromethane sulfonic acid

allyl alcohol

sodium hydride

D-glucose

→

((2R,3R,4S,5R)-6-allyloxy-3,4,5-tris-benzyloxy-tetrahydro-pyran-2-yl)-methanol

Yield 54.0%

Solvents

triethylamine

triethylamine

Conditions

Workup

1. 1
   TemperatureThe mixture was cooled down to room temperature
2. 2
   Otherthe volatiles were removed in vacuo
3. 3
   workup.DISSOLUTIONthe residue dissolved in N,N-dimethylformamide (8 L)
4. 4
   OtherThis was split into four equal reactions
5. 5
   Othereach reaction split in half
6. 6
   Othergiving eight equal reactions
7. 7
   Temperaturemaintaining the reaction temperature between 40 to 50° C
8. 8
   workup.ADDITIONAfter complete addition
9. 9
   Otherthe reaction mixtures
10. 10
    workup.STIRRINGwere stirred at room temperature for 20 hours
11. 11
    workup.ADDITIONEach reaction was then poured onto ice/water (2 L)
12. 12
    Extractionextracted with ethyl acetate (2.5 L)
13. 13
    WashThe organic phases of each were washed with saturated brine/water (1:1, 2×2 L)
14. 14
    Dryingdried over magnesium sulfate (product Rf 0.85 in 3:1 hexanes/ethyl acetate)
15. 15
    FiltrationAfter filtration and evaporation the residue
16. 16
    workup.DISSOLUTIONwas dissolved in a mixture of dichloromethane (16 L) and methanol (4 L)
17. 17
    OtherThe mixture was split into 5 equal portions
18. 18
    workup.ADDITIONto each was added sulfuric acid (32 mL)
19. 19
    workup.STIRRINGThe reactions were stirred for 3 hours
20. 20
    Washwashed with brine/2M aqueous sodium hydroxide solution (1:1, 2×2 L)
21. 21
    Dryingdried over magnesium sulfate
22. 22
    FiltrationAfter filtration and concentration in vacuo
23. 23
    Otherthe residue was further purified on silica gel eluting with 30% ethyl acetate in toluene
24. 24
    Otherto give intermediate compound (I-1a)

Procedure

A suspension of D-glucose (1.2 kg, 6.6 mol), trifluoromethane sulfonic acid (12 mL) and allyl alcohol (5 L) was heated at 80° C. for 3 days. The mixture was cooled down to room temperature, the volatiles were removed in vacuo and the residue dissolved in N,N-dimethylformamide (8 L). This was split into four equal reactions and to each was added trityl chloride (463 g, 1.67 mol) and triethylamine (231 mL, 1.67 mol). A slight exotherm was observed while adding the triethylamine. The reaction mixture was stirred for 2 days at 30° C. and then each reaction split in half, giving eight equal reactions. To each of these reactions was added benzyl chloride (300 mL, 2.60 mol), followed by portionwise addition of sodium hydride (102.5 g, 2.60 mol) maintaining the reaction temperature between 40 to 50° C. After complete addition, the reaction mixtures were stirred at room temperature for 20 hours. Each reaction was then poured onto ice/water (2 L) and extracted with ethyl acetate (2.5 L). The organic phases of each were washed with saturated brine/water (1:1, 2×2 L), combined and dried over magnesium sulfate (product Rf 0.85 in 3:1 hexanes/ethyl acetate), After filtration and evaporation the residue was dissolved in a mixture of dichloromethane (16 L) and methanol (4 L). The mixture was split into 5 equal portions and to each was added sulfuric acid (32 mL). The reactions were stirred for 3 hours, washed with brine/2M aqueous sodium hydroxide solution (1:1, 2×2 L), combined and dried over magnesium sulfate. After filtration and concentration in vacuo, the residue was further purified on silica gel eluting with 30% ethyl acetate in toluene to give intermediate compound (I-1a) as a mixture of anomers (1.77 kg, 54% yield from D-glucose). Rf 0.15 in 3:1 hexanes/ethyl acetate.

Source