1,6:2,3-Dianhydro-4-O-(2,3-di-O-benzyl-4,6-O-benzylidene-beta-D-glucopyranosyl)-beta-D-mannopyranose min. 99% synthesis

Yield:99541-22-7 275.0 g

Reaction Conditions:

Stage #1: C₁₉H₂₂O₉with sodium hydride in N,N-dimethyl-formamide;mineral oil at -15 - 20;
Stage #2: benzyl bromide in N,N-dimethyl-formamide;mineral oil at 20; for 16 h;Inert atmosphere;

Steps:

4 Step: 4 Preparation of Benzyl-Epoxide-Cellobiose (CB4)-Benzylation.

To a suspension of 78.30 grams (1958.0 mmol, 3.3 eq) of sodium hydride (60% oil) in 600 mL of dry DMF at -28°C was slowly added a solution of 234.0 grams (593 mmol, leq) of Epoxide-Anhydro-derivative (CB3) in 800 mL of dry DMF, maintaining the temperature below - 15°C. Upon completion of addition, the mixture was slowly warmed to room temperature and a solution of 211.71 mL (1780.0 mmol, 3eq) of Benzyl Bromide in 500 ml of dry DMF was added. After stirring the reaction for 16 hours at room temperature under N₂ atmosphere, TLC (40% ethyl acetate/60%heptane) analysis showed conversion of the starting material into the product. The reaction mixture was quenched in ice and extracted with ethyl acetate (2 X4 Lit), dried over sodium sulfate, filtered, and evaporated under vacuo. The residue was purified by silica gel column chromatography (10% ethyl acetate/90% heptane gradient) with 5% gradient to afford product (CB4) (275.0 g, 80%).; Conversion of Anhydrocellobiose to DC Building Block: Exact Mass: 585.2 Reagents : 1. PhCH(OMe)₂ (1.3eq), CSA (O.leq) ACN; 2.p-TosCl (3eq), DMAP, Pyridine; 3. t-BuOH , KOtBu (3eq), DCM; 4. NaH (3.3eq), BnBr (3eq), DMF; 5. NaN₃ (7eq), DMF/H₂0 (10%); 6. Ac₂0 (5eq), DCM, DMAP; 7. 80% aq TFA, THF; 8. TEMPO (l.Oeq), 10% NaOCl, DCM, H₂0, NaH₂P0₄ buffer; 9. EDC(2eq), DMAP (O.leq), Benzyl-OH (5eq), DCM

References:

WO2013/115817,2013,A1 Location in patent:Page/Page column 36; 51