ethyl 3-oxo-6-phenylmethoxyhexanoate

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

Conditions: temp:0.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: To a stirred suspension of sodium methoxide (3.48 g) in methanol (40 mL), cooled to 0° C., was added thiourea (3.56 g). The mixture was stirred until it dissolved, then 6-benzyloxy-3-oxo-hexanoic acid ethyl ester (8.52 g in 20 mL methanol) was added slowly. The solution was heated at reflux overnight, cooled to room temperature, and concentrated under vacuum. The residue was dissolved in water (50 mL), acidified to pH 6 with acetic acid, and stirred for 1 h. The precipitate was filtered, washed successively with water (2×20 mL) and isopropanol (2×20 mL), then dried to afford 6-(3-benzyloxy-propyl)-2-mercapto-pyrimidin-4-ol as a white powder (7.94 g). MS m/z 277.1 (M+1), 100%. dissolved The solution was heated at reflux overnight cooled to room temperature concentrated under vacuum The residue was dissolved in water (50 mL) stirred for 1 h The precipitate was filtered washed successively with water (2×20 mL) and isopropanol (2×20 mL) dried

Conditions: temp:0.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: To a stirred suspension of sodium methoxide (3.48 g) in methanol (40 mL), cooled to 0° C., was added thiourea (3.56 g). The mixture was stirred until it dissolved, then 6-benzyloxy-3-oxo-hexanoic acid ethyl ester (8.52 g in 20 mL methanol) was added slowly. The solution was heated at reflux overnight, cooled to room temperature, and concentrated under vacuum. The residue was dissolved in water (50 mL), acidified to pH 6 with acetic acid, and stirred for 1 h. The precipitate was filtered, washed successively with water (2×20 mL) and isopropanol (2×20 mL), then dried to afford 6-(3-benzyloxy-propyl)-2-mercapto-pyrimidin-4-ol as a white powder (7.94 g). MS m/z 277.1 (M+1), 100%. dissolved The solution was heated at reflux overnight cooled to room temperature concentrated under vacuum The residue was dissolved in water (50 mL) stirred for 1 h The precipitate was filtered washed successively with water (2×20 mL) and isopropanol (2×20 mL) dried

Conditions: temp:0.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: 4-Benzyloxybutyric acid (6.38 mL), Meldrum's acid (5.76 g) and dimethylaminopyridine (9.77 g) were dissolved in DCM (200 mL) and cooled to 0° C. A solution of isopropenyl chloroformate in dichloromethane (100 mL) was added dropwise and stirring at 0° C. continued for a further 2 h. Potassium hydrogen sulphate (200 mL of a 10% aqueous solution) was then added, the organic phase separated, dried over sodium sulphate, and evaporated under reduced pressure. The residue was dissolved in ethanol (200 mL) and heated at reflux overnight. Following cooling, the solvent was evaporated under reduced pressure and the resultant oil was purified by flash silica column chromatography. 6-Benzyloxy-3-oxo-hexanoic acid ethyl ester was isolated as an orange oil (8.53 g). the organic phase separated dried over sodium sulphate evaporated under reduced pressure The residue was dissolved in ethanol (200 mL) heated at reflux overnight Following cooling the solvent was evaporated under reduced pressure the resultant oil was purified by flash silica column chromatography

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

Conditions: temp:0.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: To a stirred solution of 13.9 g of crude 6-Benzyloxy-3-oxo-hexanoic acid ethyl ester in 50 ml dichloromethane were added dropwise 4.3 ml sulfuryl chloride. The reaction mixture was stirred at 0° C. and then at room temperature for thirty minutes. The reaction mixture was poured on ice and extracted three times with portions of 150 ml dichloromethane. The combined organic layers were washed with water, dried over MgSO4 and then the solvent was evaporated in vacuo to obtain 14.9 g of crude 6-Benzyloxy-2-chloro-3-oxo-hexanoic acid ethyl ester as a yellow oil. at room temperature for thirty minutes The reaction mixture was poured on ice extracted three times with portions of 150 ml dichloromethane The combined organic layers were washed with water dried over MgSO4 the solvent was evaporated in vacuo

Conditions: temp:0.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: To a stirred solution of 13.9 g of crude 6-Benzyloxy-3-oxo-hexanoic acid ethyl ester in 50 ml dichloromethane were added dropwise 4.3 ml sulfuryl chloride. The reaction mixture was stirred at 0° C. and then at room temperature for thirty minutes. The reaction mixture was poured on ice and extracted three times with portions of 150 ml dichloromethane. The combined organic layers were washed with water, dried over MgSO4 and then the solvent was evaporated in vacuo to obtain 14.9 g of crude 6-Benzyloxy-2-chloro-3-oxo-hexanoic acid ethyl ester as a yellow oil. at room temperature for thirty minutes The reaction mixture was poured on ice extracted three times with portions of 150 ml dichloromethane The combined organic layers were washed with water dried over MgSO4 the solvent was evaporated in vacuo

Conditions: temp:0.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: To a stirred suspension of sodium methoxide (3.48 g) in methanol (40 mL), cooled to 0° C., was added thiourea (3.56 g). The mixture was stirred until it dissolved, then 6-benzyloxy-3-oxo-hexanoic acid ethyl ester (8.52 g in 20 mL methanol) was added slowly. The solution was heated at reflux overnight, cooled to room temperature, and concentrated under vacuum. The residue was dissolved in water (50 mL), acidified to pH 6 with acetic acid, and stirred for 1 h. The precipitate was filtered, washed successively with water (2×20 mL) and isopropanol (2×20 mL), then dried to afford 6-(3-benzyloxy-propyl)-2-mercapto-pyrimidin-4-ol as a white powder (7.94 g). MS m/z 277.1 (M+1), 100%. dissolved The solution was heated at reflux overnight cooled to room temperature concentrated under vacuum The residue was dissolved in water (50 mL) stirred for 1 h The precipitate was filtered washed successively with water (2×20 mL) and isopropanol (2×20 mL) dried

Conditions: temp:0.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: 4-Benzyloxybutyric acid (6.38 mL), Meldrum's acid (5.76 g) and dimethylaminopyridine (9.77 g) were dissolved in DCM (200 mL) and cooled to 0° C. A solution of isopropenyl chloroformate in dichloromethane (100 mL) was added dropwise and stirring at 0° C. continued for a further 2 h. Potassium hydrogen sulphate (200 mL of a 10% aqueous solution) was then added, the organic phase separated, dried over sodium sulphate, and evaporated under reduced pressure. The residue was dissolved in ethanol (200 mL) and heated at reflux overnight. Following cooling, the solvent was evaporated under reduced pressure and the resultant oil was purified by flash silica column chromatography. 6-Benzyloxy-3-oxo-hexanoic acid ethyl ester was isolated as an orange oil (8.53 g). the organic phase separated dried over sodium sulphate evaporated under reduced pressure The residue was dissolved in ethanol (200 mL) heated at reflux overnight Following cooling the solvent was evaporated under reduced pressure the resultant oil was purified by flash silica column chromatography