dimethoxymethylbenzene

Conditions: temp:0.00; pressure:0.00; stir:

Conditions: temp:0.00; pressure:0.00; stir:

Conditions: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: Boron trifluoride diethyl etherate (12.56 mL, 100 mmol) was added to a −78° C. solution of N-carbobenzoxy-dl-alanine (4.47 g, 20 mmol) and benzaldehyde dimethyl acetal (2.97 mL, 19.8 mmol) in diethyl ether (100 mL). After stirring at ambient temperature for 4 days, the reaction mixture was recooled to 0° C., quenched with saturated aqueous sodium bicarbonate and extracted with diethyl ether. The combined organic extracts were dried (sodium sulfate) and concentrated in vacuo. Chromatography over silica eluting with 5-45% ethyl acetate/hexane afforded benzyl 4-methyl-5-oxo-2-phenyl-1,3-oxazolidine-3-carboxylate. was recooled to 0° C. quenched with saturated aqueous sodium bicarbonate extracted with diethyl ether The combined organic extracts were dried (sodium sulfate) concentrated in vacuo

Conditions: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: A suspension of methyl (2R,3S)-3-(9-anthracenesulfonamido)-3-phenyl-2-hydroxypropionate (II, EXAMPLE 11C, 45 mg, 0.1 mmol) in dry toluene (1 ml) is treated with benzaldehyde dimethylacetal (45 μl, 0.3 mmol) in the presence of a catalytic amount of pyndinium toluenesulfonate (2.5 mg, 0.01 mmol) and stirred at 75° under reduced pressure of 15 inch/mercury for 2 hr. HPLC analysis (silica gel with a C-18 group attached; acetonitrile/water, 65/35, flow 1 ml/min and UV 254 nm) showed the final product (70.2%, retention time 15.0 mins) and the (3S)-diasteriomer (3.5%, retention time 17.0 mins). The resulting reaction mixture is diluted with ethyl acetate (15 ml) and washed with water (10 ml). The aqueous phase is extracted again with ethyl acetate (10 ml). The combined organic phase is dried over magnesium sulfate, filtered and the solvent is removed under reduced pressure. Purification by silica gel column chromatography (ethyl acetate/hexane, 10/90) gives the title compound, mp=71-73°; IR (mineral oil) 1762, 1737, 1332, 1216, 1158, 1146, 1116, 1106, 1089, 1076, 1027, 755, 739, 697 and 681 cm−1; NMR (300 MHz, CDCl3) 9.02, 8.39, 7.86, 7.57-7.50, 7.43, 7.30-7.25, 7.07, 6.88, 6.67-6.51, 6.51-6.44, 6.27, 5.94, 4.84 and 3.77 δ; CMR (300 MHz, CDCl3) 170.0, 137.1, 136.2, 133.5, 130,9, 130.5, 128.9, 128.8, 128.6, 128.1, 128.0, 126.9, 125.2, 124.9, 93.1, 81.6, 68.7 and 52.6 δ; MS (m/z) 524 (M++1), 523 (M+), 369, 354, 346, 282,265, 241, 209, 193, 178, 165, 121 and 91; HRMS (m/z) calculated C31H25N1O5S1+H1=524.1531, observed=524.1530.

Conditions: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: A ca. 2:1 mixture of exo- and endo-isomers of bis-[(2,3-O-), (4,6-O-)]benzylidene-α-D-mannopyranoside (Carbohydrates, Ed. Collins, P. M., Chapman and Hall, New York, 1987, p. 350) was prepared by reaction of methyl α-D-mannopyranoside with 2.2 eq of α,α-dimethoxytoluene and catalytic p-toluenesulfonic acid in acetonitrile. This compound was treated with NaBH4 and HCl (Garegg, P. J.; Hultberg, H. Carbohydrate Res. 1981, 93, C10) to provide a mixture of products from which the methyl 2,6-O-benzyl-α-D-mannopyranoside was isolated by flash chromatography. The assignment of this isomer was confirmed by 1H decoupling experiments on the corresponding bis-(3,4-O-diphenylphosphino) derivative (ligand VA). 1H NMR δ7.42-7.24 (m, 10), 4.81 (d, 1, J=1 Hz), 4.75-4.54 (m, 4) 3.78-3.71 (m, 6), 3.36 (s, 3), 2.83 (bs, 1), 2.43 (bs, 1). A ca. 2:1 mixture of exo- and 1981, 93, C10) to provide was isolated by flash chromatography

Conditions: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: To a stirred solution of crude product from step 5 (1.89 g; 5.49 mmol) in a mixture of acetone (80 ml) and water (25 ml) was added p-toluene sulfonic acid monohydrate (70 mg; 0.37 mmol). After stirring at room temperature for 3 hours, triethylamine (2 ml; 1.43 mmol) was added and stirred for 5 minutes. The mixture was evaporated until volume went down to 10 ml. A mixture of acetone (80 ml) and water (15 ml) was added followed by addition of p-toluene sulfonic acid monohydrate (70 mg; 0.37 mmol). After 3.5 hours, triethylamine (3 ml; 2.15 mmol) was added, evaporated to a small volume, extracted with ether (3×100 ml). The extract was washed with brine (50 ml), dried over MgSO4 and evaporated yielding quite pure 1-hydroxyisochroman (1.3 g; 94%), (MP. 136°-138° C.). NMR (CDCl3 ; 300 MHz) δ:2.32 (3H, s, CH3O), 2.51 (1H, dd, J=12.4, 17.5 Hz, H-4), 2.97 (1H, d, J=3.5 Hz; --OH), 3.06 (1H, dd, J=4.1, 17.5 Hz, H-4), 3.77, 3.82 (3H, s each, ArOCH3), 4.70 (1H, dd, J=4.1, 12.4 Hz, H-3), 6.22 (1H, d, J=3.4 Hz, 1H), 6.71, 6.76, (1H, d each, J=9.0 Hz, ArH). stirred for 5 minutes The mixture was evaporated until volume A mixture of acetone (80 ml) and water (15 ml) was added After 3.5 hours evaporated to a small volume extracted with ether (3×100 ml) The extract was washed with brine (50 ml) dried over MgSO4 evaporated

Conditions: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: L-Ascorbic acid (20 g), α,α-dimethoxytoluene (20 g) and a catalytic quantity (160 mg) of p-toluenesulfonic acid were dissolved in 60 ml of dimethylformamide. The solution was heated at 55°-60° C. for 4 hours. The reactor used for carrying out the reaction was equipped with a reflux-condenser connected to an aspirator, and the methanol formed during the reaction process produces was evaporated out of the reaction mixture. When the reaction was completed, the reaction solution was distilled under reduced pressure to remove the solvent. The resulting syrupy residue was washed with petroleum ether and water, each three times. Then, water and hexane were added to the washed syrup and the mixture was stirred to obtain a crystalline product of 5,6-O-benzylidene-L-ascorbic acid which was then filtrated off and dried to give 21.5 g of white colored crystals of 5,6-O-benzylidene-L-ascorbic acid (72% yield). The product thus obtained was nearly pure substance but was further purified by recrystallization from methanol or benzene. The final pure crystal showed mp. of 166°-168° C. The solution was heated at 55°-60° C. for 4 hours was equipped with a reflux-condenser produces was evaporated out of the reaction mixture the reaction solution was distilled under reduced pressure to remove the solvent The resulting syrupy residue was washed with petroleum ether and water Then, water and hexane were added to the washed syrup

Conditions: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: L-Ascorbic acid (20 g), α,α-dimethoxytoluene (20 g) and a catalytic quantity (160 mg) of p-toluenesulfonic acid were dissolved in 60 ml of dimethylformamide. The solution was heated at 55°-60° C. for 4 hours. The reactor used for carrying out the reaction was equipped with a reflux-condenser connected to an aspirator, and the methanol formed during the reaction process produces was evaporated out of the reaction mixture. When the reaction was completed, the reaction solution was distilled under reduced pressure to remove the solvent. The resulting syrupy residue was washed with petroleum ether and water, each three times. Then, water and hexane were added to the washed syrup and the mixture was stirred to obtain a crystalline product of 5,6-O-benzylidene-L-ascorbic acid which was then filtrated off and dried to give 21.5 g of white colored crystals of 5,6-O-benzylidene-L-ascorbic acid (72% yield). The product thus obtained was nearly pure substance but was further purified by recrystallization from methanol or benzene. The final pure crystal showed mp. of 166°-168° C. The solution was heated at 55°-60° C. for 4 hours was equipped with a reflux-condenser produces was evaporated out of the reaction mixture the reaction solution was distilled under reduced pressure to remove the solvent The resulting syrupy residue was washed with petroleum ether and water Then, water and hexane were added to the washed syrup

Conditions: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: To a solution of (1S,2S,3S,4R,5S)-5-(4-chloro-3-(4-ethoxybenzyl)phenyl)-1-(hydroxymethyl)-6,8-dioxabicyclo[3.2.1]octane-2,3,4-triol 28a (11.93 g, 27.3 mmol, purchased from Shanghai Caerulum Pharma Discovery Co., Ltd) in acetonitrile (40 mL) were added benzaldehyde dimethyl acetal (12.3 mL, 81.9 mmol) and p-toluenesulfonic acid monohydrate (4.7 g, 27.3 mmol) at room temperature. The mixture was stirred at room temperature for 30 min and adjusted with saturated aqueous sodium bicarnonate till pH becomes 7. The resulting mixture was extracted with ethyl actate (50 mL×2). The combined organic phases were washed with saturated aqueous sodium chloride (30 mL×2), dried over anhydrous sodium sulfate and filtered. The filtrate was concentrated in vacuo and the residue was purified by silica gel chromatography eluted with PE/EtOAc(v/v)=5/1 to give the title compound 28b as a white solid (14.3 g, 100%). The resulting mixture was extracted with ethyl actate (50 mL×2) The combined organic phases were washed with saturated aqueous sodium chloride (30 mL×2) dried over anhydrous sodium sulfate filtered The filtrate was concentrated in vacuo the residue was purified by silica gel chromatography eluted with PE/EtOAc(v/v)=5/1

Conditions: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: To a solution of (1S,2S,3S,4R,5S)-5-(4-chloro-3-(4-ethoxybenzyl)phenyl)-1-(hydroxymethyl)-6,8-dioxabicyclo[3.2.1]octane-2,3,4-triol 28a (11.93 g, 27.3 mmol, purchased from Shanghai Caerulum Pharma Discovery Co., Ltd) in acetonitrile (40 mL) were added benzaldehyde dimethyl acetal (12.3 mL, 81.9 mmol) and p-toluenesulfonic acid monohydrate (4.7 g, 27.3 mmol) at room temperature. The mixture was stirred at room temperature for 30 min and adjusted with saturated aqueous sodium bicarnonate till pH becomes 7. The resulting mixture was extracted with ethyl actate (50 mL×2). The combined organic phases were washed with saturated aqueous sodium chloride (30 mL×2), dried over anhydrous sodium sulfate and filtered. The filtrate was concentrated in vacuo and the residue was purified by silica gel chromatography eluted with PE/EtOAc(v/v)=5/1 to give the title compound 28b as a white solid (14.3 g, 100%). The resulting mixture was extracted with ethyl actate (50 mL×2) The combined organic phases were washed with saturated aqueous sodium chloride (30 mL×2) dried over anhydrous sodium sulfate filtered The filtrate was concentrated in vacuo the residue was purified by silica gel chromatography eluted with PE/EtOAc(v/v)=5/1

Conditions: temp:45.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: To a 300 mL-volume Kjeldahl flask, 50 g of benzaldehyde dimethyl acetal and 27.08 g of acetyl chloride were added, and the mixture was stirred at 45° C. for 3 hours. After the reaction, the low boiling point residue was removed under reduced pressure to obtain 49.8 g of α-chlorobenzyl methyl ether. After the reaction the low boiling point residue was removed under reduced pressure

Conditions: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: Using a modification of the procedure as described: Tetrahedron, 1992, 48(47), 10249-10264. Methyl β-D-glucopyranoside (Biosynth International M-3592; 10.2 g, 50 mmol), benzaldehyde dimethylacetal (30 ml, 200 mmol) and 10-camphorsulfonic acid (116 mg, 0.5 mmol) in anhydrous acetonitrile (150 ml) was stirred at room temperature for 4 h. The reaction was checked by TLC to confirm complete conversion to the product (run in hexane: ethyl acetate, 1:2, visualised with ceric ammonium molybdate spray and heating. The reaction was then treated with triethylamine (1 ml) to neutralise the acid. The solution was filtered and the solid was washed with acetonitrile (20 ml). The mother solution was concentrated to about 60 ml, and it was again filtrated, and the filtrate washed with acetonitdrile (10 ml). The combined solid was dried in vacuum, to give 12.9 g (91%) of methyl 4,6-O-benzylidene-β-D-glucopyranoside. heating The solution was filtered the solid was washed with acetonitrile (20 ml) The mother solution was concentrated to about 60 ml, and it was again filtrated the filtrate washed with acetonitdrile (10 ml) The combined solid was dried in vacuum