2,2-diethoxyethanol

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

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: Hydroxyacetaldehyde diethylacetal (3.75 g) was added to sodium hydride (0.8 g, 80% in mineral oil) in tetrahydrofuran (100 ml) under an atmosphere of nitrogen. The mixture was stirred and bromoacetaldehyde diethyl acetal (5.0 g) and potassium iodide (0.1 g) were added. The mixture was heated to reflux for 16 hours, water added and evaporated under reduced pressure. The residue was dissolved in diethyl ether, the organic phase washed with water, dried (MgSO4) and evaporated under reduced pressure to give bis(2,2-diethoxyethyl)ether, 3.43 g, as a yellow oil. The mixture was heated to reflux for 16 hours evaporated under reduced pressure The residue was dissolved in diethyl ether the organic phase washed with water dried (MgSO4) evaporated under reduced pressure

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

Procedure: Hydroxyacetaldehyde diethylacetal (3.75 g) was added to sodium hydride (0.8 g, 80% in mineral oil) in tetrahydrofuran (100 ml) under an atmosphere of nitrogen. The mixture was stirred and bromoacetaldehyde diethyl acetal (5.0 g) and potassium iodide (0.1 g) were added. The mixture was heated to reflux for 16 hours, water added and evaporated under reduced pressure. The residue was dissolved in diethyl ether, the organic phase washed with water, dried (MgSO4) and evaporated under reduced pressure to give bis(2,2-diethoxyethyl)ether, 3.43 g, as a yellow oil. The mixture was heated to reflux for 16 hours evaporated under reduced pressure The residue was dissolved in diethyl ether the organic phase washed with water dried (MgSO4) evaporated under reduced pressure

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

Procedure: To a pyridine (30 ml) solution of glycol aldehyde diethylacetal (19.8 g, 148 mmol), benzoyl chloride (51.7 ml, 444 mmol) was added dropwise at −20 to 30° C. The mixture was stirred at room temperature for 167 hours and 50 minutes. After methanol and water were added to the mixture, extraction with ethyl acetate was performed. The obtained organic layer was washed with a saturated aqueous ammonium chloride solution, saturated aqueous sodium hydrogencarbonate solution, and a saturated saline solution. After dried over anhydrous magnesium sulfate, the mixture was concentrated under reduced pressure and purified by silica gel column chromatography (elution solvent: heptane, ethyl acetate/heptane=1/9). Thereafter, purification by silica gel column chromatography (elution solvent: heptane, ethyl acetate/heptane=1/100, 1/30, 1/10) was performed again to obtain the title compound (34 g, yield: 96.4%) as a light green oil. The obtained organic layer was washed with a saturated aqueous ammonium chloride solution, saturated aqueous sodium hydrogencarbonate solution After dried over anhydrous magnesium sulfate the mixture was concentrated under reduced pressure purified by silica gel column chromatography (elution solvent: heptane, ethyl acetate/heptane=1/9) Thereafter, purification by silica gel column chromatography (elution solvent: heptane, ethyl acetate/heptane=1/100, 1/30, 1/10)

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

Procedure: 2,2-Diethoxyethanol (1.6 g) and cesium carbonate (5.8 g) were added to DMF solution (10 mL) of 5-bromo-2-chloropyrimidine (1.15 g), and stirred at room temperature for 12 hours. After addition of water, the reaction liquid was extracted with ethyl acetate and dried over anhydrous magnesium sulfate. Concentrating the solvent under reduced pressure, the residue was purified on silica gel column chromatography (C-200; ethyl acetate:hexane=1:9-1:4) to provide the title compound (1.63 g, 94%). the reaction liquid was extracted with ethyl acetate dried over anhydrous magnesium sulfate Concentrating the solvent under reduced pressure the residue was purified on silica gel column chromatography (C-200; ethyl acetate:hexane=1:9-1:4)

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

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

Procedure: To a pyridine (30 ml) solution of glycol aldehyde diethylacetal (19.8 g, 148 mmol), benzoyl chloride (51.7 ml, 444 mmol) was added dropwise at −20 to 30° C. The mixture was stirred at room temperature for 167 hours and 50 minutes. After methanol and water were added to the mixture, extraction with ethyl acetate was performed. The obtained organic layer was washed with a saturated aqueous ammonium chloride solution, saturated aqueous sodium hydrogencarbonate solution, and a saturated saline solution. After dried over anhydrous magnesium sulfate, the mixture was concentrated under reduced pressure and purified by silica gel column chromatography (elution solvent: heptane, ethyl acetate/heptane=1/9). Thereafter, purification by silica gel column chromatography (elution solvent: heptane, ethyl acetate/heptane=1/100, 1/30, 1/10) was performed again to obtain the title compound (34 g, yield: 96.4%) as a light green oil. The obtained organic layer was washed with a saturated aqueous ammonium chloride solution, saturated aqueous sodium hydrogencarbonate solution After dried over anhydrous magnesium sulfate the mixture was concentrated under reduced pressure purified by silica gel column chromatography (elution solvent: heptane, ethyl acetate/heptane=1/9) Thereafter, purification by silica gel column chromatography (elution solvent: heptane, ethyl acetate/heptane=1/100, 1/30, 1/10)

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

Procedure: 2,2-Diethoxyethanol (1.6 g) and cesium carbonate (5.8 g) were added to DMF solution (10 mL) of 5-bromo-2-chloropyrimidine (1.15 g), and stirred at room temperature for 12 hours. After addition of water, the reaction liquid was extracted with ethyl acetate and dried over anhydrous magnesium sulfate. Concentrating the solvent under reduced pressure, the residue was purified on silica gel column chromatography (C-200; ethyl acetate:hexane=1:9-1:4) to provide the title compound (1.63 g, 94%). the reaction liquid was extracted with ethyl acetate dried over anhydrous magnesium sulfate Concentrating the solvent under reduced pressure the residue was purified on silica gel column chromatography (C-200; ethyl acetate:hexane=1:9-1:4)

Conditions: temp:30.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: 2,2-Diethoxy-ethanol (0.209 g, 1.2135 mmol) was added to a cooled suspension of NaH (0.034 g, 1.456 mmol) in THF (5 mL) at 0° C. and the resulting mixture was stirred for 30 minutes at 20-40° C. 2-Fluoro-4-iodo-phenyl-(2,3,5-trifluoro-6-nitro-phenyl)-amine (0.5 g, 1.2135 mmol) in THF (10 mL) was added slowly to the reaction mass at 0° C. and stirring was continued for a further 15 minutes. The reaction mass was stirred overnight at room temperature. The reaction was monitored by TLC (20% ethyl acetate in hexane). The reaction mass was concentrated under reduced pressure and the concentrate was extracted with ethyl acetate. The organic layer was washed with water, brine solution, dried over sodium sulphate and concentrated under reduced pressure to afford the crude compound. Purification by column chromatography on silica gel (15% ethyl acetate in hexane) afforded 0.3 g of the product (47% yield). 1H NMR (CDCl3, 300 MHz): δ 7.42 (d, 1H), 7.35 (d, 1H), 6.90 (bs, 1H), 6.58-6.68 (m, 2H), 4.58 (t, 1H), 4.15 (d, 2H), 3.51-3.80 (m, 4H), 1.22 (t, 6H). stirring was continued for a further 15 minutes The reaction mass was stirred overnight at room temperature The reaction mass was concentrated under reduced pressure the concentrate was extracted with ethyl acetate The organic layer was washed with water, brine solution dried over sodium sulphate concentrated under reduced pressure to afford the crude compound Purification by column chromatography on silica gel (15% ethyl acetate in hexane)

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

Procedure: With cooling with ice, a tetrahydrofuran solution (2 ml) of 2,2-diethoxyethanol (668 mg, 4.98 mmol) was added to a mixed tetrahydrofuran (4 ml)/N,N-dimethylacetamide (2 ml) solution of 2-chloro-5-fluoropyrimidine (600 mg, 4.53 mmol), and stirred under a nitrogen atmosphere for 1 hour. Water was added to the reaction solution, and extracted with ethyl acetate. Next, the organic layer was washed with saturated saline water, dried over anhydrous sodium sulfate, and concentrated under reduced pressure. The obtained residue was purified by silica gel column chromatography (Moritex, acetone:hexane=1:25) to obtain 2-(2,2-diethoxyethoxy)-5-fluoropyrimidine (699 mg, yield: 67%) as a colorless oil, and 2-chloro-5-(2,2-diethoxyethoxy)pyrimidine (233 mg, 21%) as a colorless solid. With cooling with ice extracted with ethyl acetate Next, the organic layer was washed with saturated saline water dried over anhydrous sodium sulfate concentrated under reduced pressure The obtained residue was purified by silica gel column chromatography (Moritex, acetone:hexane=1:25)