1-phenylmethoxypropan-2-one

Conditions: temp:65.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: 3-Benzyoxypropan-2-ol 16 (40 g, 0.24 mol) was added to a suspension of pyridinium chlorochromate (155.2 g, 0.72 mol) in DMF (150 ml) at 25° C., stirred at 65° C. for 3 h, and then diluted with water (75 mL) (Step 14). The mixture was extracted with ether (2×50 mL) and the combined ether layers were washed with water (3×50 mL) dried (MgSO4) and the solvent removed by roto-evaporation. Distillation gave 31 g (77%) of 3-benzyloxypropan-2-one; 17 bp 104-106 (10 mm). 1H NMR (CDCl3) δ2.16 (s, 3H, CH3), 4.05 (s, 1H, OH), 4.59 (s, 2H, OCH2), 7.5 (s, 5H, phenyl). The mixture was extracted with ether (2×50 mL) the combined ether layers were washed with water (3×50 mL) dried (MgSO4) the solvent removed by roto-evaporation Distillation

Conditions: temp:65.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: 3-Benzyoxypropan-2-ol 16 (40 g, 0.24 mol) was added to a suspension of pyridinium chlorochromate (155.2 g, 0.72 mol) in DMF (150 ml) at 25° C., stirred at 65° C. for 3 h, and then diluted with water (75 mL) (Step 14). The mixture was extracted with ether (2×50 mL) and the combined ether layers were washed with water (3×50 mL) dried (MgSO4) and the solvent removed by roto-evaporation. Distillation gave 31 g (77%) of 3-benzyloxypropan-2-one; 17 bp 104-106 (10 mm). 1H NMR (CDCl3) δ2.16 (s, 3H, CH3), 4.05 (s, 1H, OH), 4.59 (s, 2H, OCH2), 7.5 (s, 5H, phenyl). The mixture was extracted with ether (2×50 mL) the combined ether layers were washed with water (3×50 mL) dried (MgSO4) the solvent removed by roto-evaporation Distillation

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

Procedure: A mixture of 1-benzyloxy-2-propanone (4.94 g, 30.1 mmol), ethylene glycol (20 ml, 359 mmol), triethyl orthoformate (5 ml, 30.1 mmol), and p-toluenesulfonic acid monohydrate (130 mg, 0.683 mmol) was stirred at room temperature for 61.5 hours. To the reaction mixture, a saturated aqueous sodium hydrogen carbonate solution (20 ml) was added and the mixture was extracted twice with chloroform (50 ml) and the organic layer was dried over anhydrous sodium sulfate and concentrated. The crude product was purified by silica gel column chromatography (NH silica gel, elution solvent: heptane/ethyl acetate=1/0 to 4/1 gradient). Desired fractions were concentrated to obtain the title compound (5.67 g, 90.5% yield) as a colorless oil. the mixture was extracted twice with chloroform (50 ml) the organic layer was dried over anhydrous sodium sulfate concentrated The crude product was purified by silica gel column chromatography (NH silica gel, elution solvent: heptane/ethyl acetate=1/0 to 4/1 gradient) Desired fractions were concentrated

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

Procedure: The same procedure as in the steps (32a) and (32b) of Example 32 was repeated using 1-benzyloxy-2-propanone to obtain the title compound (1.51 g, total yield: 37%) as a light yellow oil.

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

Procedure: A mixture of 1-benzyloxy-2-propanone (4.94 g, 30.1 mmol), ethylene glycol (20 ml, 359 mmol), triethyl orthoformate (5 ml, 30.1 mmol), and p-toluenesulfonic acid monohydrate (130 mg, 0.683 mmol) was stirred at room temperature for 61.5 hours. To the reaction mixture, a saturated aqueous sodium hydrogen carbonate solution (20 ml) was added and the mixture was extracted twice with chloroform (50 ml) and the organic layer was dried over anhydrous sodium sulfate and concentrated. The crude product was purified by silica gel column chromatography (NH silica gel, elution solvent: heptane/ethyl acetate=1/0 to 4/1 gradient). Desired fractions were concentrated to obtain the title compound (5.67 g, 90.5% yield) as a colorless oil. the mixture was extracted twice with chloroform (50 ml) the organic layer was dried over anhydrous sodium sulfate concentrated The crude product was purified by silica gel column chromatography (NH silica gel, elution solvent: heptane/ethyl acetate=1/0 to 4/1 gradient) Desired fractions were concentrated

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

Procedure: The same procedure as in the steps (32a) and (32b) of Example 32 was repeated using 1-benzyloxy-2-propanone to obtain the title compound (1.51 g, total yield: 37%) as a light yellow oil.

Conditions: temp:65.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: 3-Benzyoxypropan-2-ol 16 (40 g, 0.24 mol) was added to a suspension of pyridinium chlorochromate (155.2 g, 0.72 mol) in DMF (150 ml) at 25° C., stirred at 65° C. for 3 h, and then diluted with water (75 mL) (Step 14). The mixture was extracted with ether (2×50 mL) and the combined ether layers were washed with water (3×50 mL) dried (MgSO4) and the solvent removed by roto-evaporation. Distillation gave 31 g (77%) of 3-benzyloxypropan-2-one; 17 bp 104-106 (10 mm). 1H NMR (CDCl3) δ 2.16 (s, 3H, CH3), 4.05 (s, 1H, OH), 4.59 (s, 2H, OCH2), 7.5 (s, 5H, phenyl). The mixture was extracted with ether (2×50 mL) the combined ether layers were washed with water (3×50 mL) dried (MgSO4) the solvent removed by roto-evaporation Distillation

Conditions: temp:65.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: 3-Benzyoxypropan-2-ol 16 (40 g, 0.24 mol) was added to a suspension of pyridinium chlorochromate (155.2 g, 0.72 mol) in DMF (150 ml) at 25° C., stirred at 65° C. for 3 h, and then diluted with water (75 mL) (Step 14). The mixture was extracted with ether (2×50 mL) and the combined ether layers were washed with water (3×50 mL) dried (MgSO4) and the solvent removed by roto-evaporation. Distillation gave 31 g (77%) of 3-benzyloxypropan-2-one; 17 bp 104-106 (10 mm). 1H NMR (CDCl3) δ 2.16 (s, 3H, CH3), 4.05 (s, 1H, OH), 4.59 (s, 2H, OCH2), 7.5 (s, 5H, phenyl). The mixture was extracted with ether (2×50 mL) the combined ether layers were washed with water (3×50 mL) dried (MgSO4) the solvent removed by roto-evaporation Distillation

Conditions: temp:65.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: 3-Benzyoxypropan-2-ol 16 (40 g, 0.24 mol) was added to a suspension of pyridinium chlorochromate (155.2 g, 0.72 mol) in DMF (150 ml) at 25° C., stirred at 65° C. for 3 h, and then diluted with water (75 mL) (Step 14). The mixture was extracted with ether (2×50 mL) and the combined ether layers were washed with water (3×50 mL) dried (MgSO4) and the solvent removed by roto-evaporation. Distillation gave 31 g (77%) of 3-benzyloxypropan-2-one; 17 bp 104-106 (10 mm). 1H NMR (CDCl3) δ 2.16 (s, 3H, CH3), 4.05 (s, 1H, OH), 4.59 (s, 2H, OCH2), 7.5 (s, 5H, phenyl). The mixture was extracted with ether (2×50 mL) the combined ether layers were washed with water (3×50 mL) dried (MgSO4) the solvent removed by roto-evaporation Distillation

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

Procedure: 5.07 g (27.79 mmol) of 1-(benzyloxy)acetone were initially charged in 55.6 ml of 2 N aqueous ammonia in methanol, 1.53 g (31.12 mmol) of sodium cyanide and 3.71 g (31.12 mmol) of ammonium chloride were added and the mixture was heated under reflux for 2 h. Another 27.4 ml of 2 N aqueous ammonia in methanol were then added, and the reaction mixture was stirred under reflux for 2 h. The reaction solution was cooled and diluted with 90 ml of dichloromethane. The solid obtained was filtered off and the filtrate was concentrated. The residue was purified using silica gel (mobile phase: cyclohexane/ethyl acetate gradient: from 4/1 to 1/1). This gave 4.94 g of the target compound (90% pure, 84% of theory). the mixture was heated under reflux for 2 h under reflux for 2 h The reaction solution was cooled The solid obtained was filtered off the filtrate was concentrated The residue was purified

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

Procedure: The product of Example 4 Step A and 1-(benzyloxy)acetone were combined in a procedure similar to Example 4 Step B to obtain the title compound.

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

Procedure: A mixture of 1-benzyloxy-2-propanone (4.94 g, 30.1 mmol), ethylene glycol (20 ml, 359 mmol), triethyl orthoformate (5 ml, 30.1 mmol), and p-toluenesulfonic acid monohydrate (130 mg, 0.683 mmol) was stirred at room temperature for 61.5 hours. To the reaction mixture, a saturated aqueous sodium hydrogen carbonate solution (20 ml) was added and the mixture was extracted twice with chloroform (50 ml) and the organic layer was dried over anhydrous sodium sulfate and concentrated. The crude product was purified by silica gel column chromatography (NH silica gel, elution solvent: heptane/ethyl acetate=1/0 to 4/1 gradient). Desired fractions were concentrated to obtain the title compound (5.67 g, 90.5% yield) as a colorless oil. the mixture was extracted twice with chloroform (50 ml) the organic layer was dried over anhydrous sodium sulfate concentrated The crude product was purified by silica gel column chromatography (NH silica gel, elution solvent: heptane/ethyl acetate=1/0 to 4/1 gradient) Desired fractions were concentrated