ETHYL 2-O-BENZOYL-4,6-O-BENZYLIDENE-BETA-D-GALACTOPYRANOSIDE synthesis

Yield:161765-88-4 1.7 g (48 %)

Reaction Conditions:

with pyridine;ammonia in methanol;dichloromethane;

Steps:

1 Ethyl 4,6-O-benzylidene-2-O-benzoyl-β-D-galactospyranoside (6) and Ethyl 4,6-O-benzylidene-3-O-(trichloroacetyl-N-carbamoyl)-2-O-benzoyl-β-D-galactospyranoside (Compound 7)

EXAMPLE 1 Ethyl 4,6-O-benzylidene-2-O-benzoyl-β-D-galactospyranoside (6) and Ethyl 4,6-O-benzylidene-3-O-(trichloroacetyl-N-carbamoyl)-2-O-benzoyl-β-D-galactospyranoside (Compound 7) Ethyl 4,6-O-benzylidene-β-D-galactopyranoside Compound 5, [Wallenfels et al., Justis Liebigs Ann. Chem., 635:166 (1960)] (2.9 g, 9.8 mmol) was dissolved in CH₂ Cl₂ (29 mL) and pyridine (5.4 mL) and cooled to -65° C. under argon. Chloroacetic anhydride (0.82 mL, 10.3 mmol) was then added and the reaction mixture was stirred at -65° C. for two hours. The first stage of the reaction was complete at this time, and benzoyl chloride (1.36 mL, 11.78 mmoles) was then added at -65° C. The reaction mixture was permitted to warm to room temperature, stirred overnight (about 18 hours), diluted with CH₂ Cl₂ (100 mL), and washed with 1M citric acid (100 mL), water (50 mL), saturated NaHCO₃ (50 mL), water (50 mL), and saturated NaCl₍₅₀ mL). The organic layer was dried (Na₂ SO₄), filtered and concentrated to afford a crude 2-benzoyl-3-chloroacetyl product. The crude product was then dissolved in methanol (50 mL) and cooled to -30° C. A solution of 2M NH₃ in methanol (6.0 mL) was added and the reaction stirred at -30° C. for four hours to selectively cleave the chloroacetyl group. The resulting mixture was poured into CH₂ Cl₂ (100 mL) and washed with water (100 mL), saturated NaHCO₃ (100 mL), water (100 mL), and saturated NaCl (50 mL). The organic solution was dried (Na₂ SO₄), filtered, concentrated and chromatographed (silica, 80 percent ethyl acetate/hexane) to afford 1.7 g (48 percent) of Compound 6 as a white solid. R_f =0.3 (silica, ethyl acetate/hexane); ¹ H NMR (CDCl₃) δ8.07 (d, J=7.5 Hz, 2H, arom.), 7.55 (m, 3H, arom.), 7.46 (d, J=7.5 Hz, 2H, arom.), 7.38 (m, 3H, aromatic), 5.59 (s, 1H, benzylidene), 5.36 (dd, J=10.07, 8.2 Hz, 1H, H-2), 4.64 (d, J=8.2 Hz, 1H, H-1), 4.39 (dd, J=12.5, 1.1 Hz, 1H, H-6), 4.28 (d, J=4.0 Hz, 1H, H-4), 4.12 (dd, J=1.5, 12.5 Hz, 1H, H-6), 3.99-3.86 (multiple peaks, 2H, OCH₂ CH₃, H-3), 3.61 (m, 1H, OCH₂ CH₃), 3.56 (bs, 1H, H-5), 2.63 (d, J=9.0 Hz, 1H, OH), 1.21 (t, 3H, CH₃).

References:

US5559103,1996,A