4-C-(Iodomethyl)-1,2-di-O-(1-methylethylidene)-3,5-bis-O-(phenylmethyl)--D-ribofuranose synthesis

Yield:-

Reaction Conditions:

with 1H-imidazole;iodine;triphenylphosphine in 1,4-dioxane;benzene at 85; for 60 h;

Steps:

1.H Step H

Step H 1,2-O-isopropylidene-3,5-di-O-benzyl-4-C-iodomethyl-α-D-ribofuranose Iodine (14.2 g, 55.83 mmol) was added to a solution of 1,2-O-isopropylidene-3,5-di-O-benzyl-4-hydroxymethyl-α-D-ribofuranose (11.51 g, 28.78 mmol), triphenylphosphine (29.17 g, 111.22 mmol), and imidazole (7.56 g, 111.06 mmol) in a mixture of dry benzene (120 mL) and dry 1,4-dioxane (30 mL). The reaction mixture was stirred at 85° C. under N₂ atmosphere for 24 h. Additional portions of triphenylphosphine (9.72 g), imidazole (2.52 g) and iodine (4.73 g) were added and the stirring was continued for total of 36 h. The reaction mixture was concentrated into a crude residue which was poured into 10% Na₂S₂O₃ solution and extracted with ethyl acetate. The organic layer was washed with saturated aqueous NaHCO₃ solution, saturated brine solution, dried (MgSO₄) and concentrated to a crude residue, which was applied to a column of silica gel eluted with hexane-ethyl acetate (4:1) to give the title compound as a syrup. ¹H NMR (CD₂Cl₂, 200 MHz): δ 7.35-7.32 (m, 5H, ArH), 5.72 (d, 1H, J=3.8Hz, H-1), 4.75-4.54 (m, 5H, H-2, 2 OCH₂Ph), 4.28 (d, 1H, J=5.0Hz, H-3), 3.93 (d, 1H, J_gem=11.2 Hz, CHI), 3.55 (dd, 2H, CH₂OBn), 3.49 (d, 1H, J_gem=11.2Hz, CHI), 1.59 (s, 3H, CH₃), 1.33 (s, 3H, CH₃). ¹³C NMR (CD₂Cl₂, 50 MHz): δ 138.32, 137.92, 128.56, 128.53, 128.08, 128.00, 127.96, 127.87, 113.67, 109.99, 103.78, 83.93, 79.34, 74.70, 73.80, 72.79, 26.89, 25.96, 11.34.

References:

US2004/229840,2004,A1 Location in patent:Page 12