methyl 3-(3-methoxy-3-oxopropyl)sulfanylpropanoate

Conditions: temp:25.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: A solution of dimethyl 3,3′-thiodipropionate (30.00 g, 144.0 mmol) in ethylene glycol dimethyl ether (200 mL), under nitrogen, was treated with sodium hydride (7.00 g, 145.8 mmol), and the reaction was heated under reflux for 1.5 h. The reaction mixture was then cooled to 25° C. and was slowly treated with a saturated aqueous sodium bicarbonate solution. The solvent was then removed in vacuo, and the resulting residue was diluted with water (500 mL) and extracted with ethyl acetate 3×300 mL). The combined organic extracts were then washed with a saturated aqueous sodium bicarbonate solution (1×150 mL) followed by a saturated aqueous sodium chloride solution (1×150 mL). The organic layer was dried over magnesium sulfate, filtered, and concentrated in vacuo. Biotage chromatography, performed in two batches, (FLASH 40M, Silica, 9/1 hexanes/diethyl ether) afforded 4-hydroxy-5,6-dihydro-2H-thiopyran-3-carboxylic acid methyl ester (12.89 g, 51.4%) as a colorless oil. the reaction was heated under reflux for 1.5 h The solvent was then removed in vacuo the resulting residue was diluted with water (500 mL) extracted with ethyl acetate 3×300 mL) The combined organic extracts were then washed with a saturated aqueous sodium bicarbonate solution (1×150 mL) The organic layer was dried over magnesium sulfate filtered concentrated in vacuo

Conditions: temp:25.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: A solution of dimethyl 3,3′-thiodipropionate (30.00 g, 144.0 mmol) in ethylene glycol dimethyl ether (200 mL), under nitrogen, was treated with sodium hydride (7.00 g, 145.8 mmol), and the reaction was heated under reflux for 1.5 h. The reaction mixture was then cooled to 25° C. and was slowly treated with a saturated aqueous sodium bicarbonate solution. The solvent was then removed in vacuo, and the resulting residue was diluted with water (500 mL) and extracted with ethyl acetate 3×300 mL). The combined organic extracts were then washed with a saturated aqueous sodium bicarbonate solution (1×150 mL) followed by a saturated aqueous sodium chloride solution (1×150 mL). The organic layer was dried over magnesium sulfate, filtered, and concentrated in vacuo. Biotage chromatography, performed in two batches, (FLASH 40M, Silica, 9/1 hexanes/diethyl ether) afforded 4-hydroxy-5,6-dihydro-2H-thiopyran-3-carboxylic acid methyl ester (12.89 g, 51.4%) as a colorless oil. the reaction was heated under reflux for 1.5 h The solvent was then removed in vacuo the resulting residue was diluted with water (500 mL) extracted with ethyl acetate 3×300 mL) The combined organic extracts were then washed with a saturated aqueous sodium bicarbonate solution (1×150 mL) The organic layer was dried over magnesium sulfate filtered concentrated in vacuo

Conditions: temp:25.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: A solution of dimethyl 3,3′-thiodipropionate (30.00 g, 144.0 mmol) in ethylene glycol dimethyl ether (200 mL), under nitrogen, was treated with sodium hydride (7.00 g, 145.8 mmol), and the reaction was heated under reflux for 1.5 h. The reaction mixture was then cooled to 25° C. and was slowly treated with a saturated aqueous sodium bicarbonate solution. The solvent was then removed in vacuo, and the resulting residue was diluted with water (500 mL) and extracted with ethyl acetate (3×300 mL). The combined organic extracts were then washed with a saturated aqueous sodium bicarbonate solution (1×150 mL) followed by a saturated aqueous sodium chloride solution (1×150 mL). The organic layer was dried over magnesium sulfate, filtered, and concentrated in vacuo. Biotage chromatography, performed in two batches, (FLASH 40M, Silica, 9/1 hexanes/diethyl ether) afforded 4-hydroxy-5,6-dihydro-2H-thiopyran-3-carboxylic acid methyl ester (12.89 g, 51.4%) as a colorless oil. the reaction was heated under reflux for 1.5 h The solvent was then removed in vacuo the resulting residue was diluted with water (500 mL) extracted with ethyl acetate (3×300 mL) The combined organic extracts were then washed with a saturated aqueous sodium bicarbonate solution (1×150 mL) The organic layer was dried over magnesium sulfate filtered concentrated in vacuo

Conditions: temp:25.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: A solution of dimethyl 3,3′-thiodipropionate (30.00 g, 144.0 mmol) in ethylene glycol dimethyl ether (200 mL), under nitrogen, was treated with sodium hydride (7.00 g, 145.8 mmol), and the reaction was heated under reflux for 1.5 h. The reaction mixture was then cooled to 25° C. and was slowly treated with a saturated aqueous sodium bicarbonate solution. The solvent was then removed in vacuo, and the resulting residue was diluted with water (500 mL) and extracted with ethyl acetate (3×300 mL). The combined organic extracts were then washed with a saturated aqueous sodium bicarbonate solution (1×150 mL) followed by a saturated aqueous sodium chloride solution (1×150 mL). The organic layer was dried over magnesium sulfate, filtered, and concentrated in vacuo. Biotage chromatography, performed in two batches, (FLASH 40M, Silica, 9/1 hexanes/diethyl ether) afforded 4-hydroxy-5,6-dihydro-2H-thiopyran-3-carboxylic acid methyl ester (12.89 g, 51.4%) as a colorless oil. the reaction was heated under reflux for 1.5 h The solvent was then removed in vacuo the resulting residue was diluted with water (500 mL) extracted with ethyl acetate (3×300 mL) The combined organic extracts were then washed with a saturated aqueous sodium bicarbonate solution (1×150 mL) The organic layer was dried over magnesium sulfate filtered concentrated in vacuo

Conditions: temp:25.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: A solution of dimethyl 3,3′-thiodipropionate (30.00 g, 144.0 mmol) in ethylene glycol dimethyl ether (200 mL), under nitrogen, was treated with sodium hydride (7.00 g, 145.8 mmol), and the reaction was heated under reflux for 1.5 h. The reaction mixture was then cooled to 25° C. and was slowly treated with a saturated aqueous sodium bicarbonate solution. The solvent was then removed in vacuo, and the resulting residue was diluted with water (500 mL) and extracted with ethyl acetate (3×300 mL). The combined organic extracts were then washed with a saturated aqueous sodium bicarbonate solution (1×150 mL) followed by a saturated aqueous sodium chloride solution (1×150 mL). The organic layer was dried over magnesium sulfate, filtered, and concentrated in vacuo. Biotage chromatography, performed in two batches, (FLASH 40M, Silica, 9/1 hexanes/diethyl ether) afforded 4-hydroxy-5,6-dihydro-2H-thiopyran-3-carboxylic acid methyl ester (12.89 g, 51.4%) as a colorless oil. the reaction was heated under reflux for 1.5 h The solvent was then removed in vacuo the resulting residue was diluted with water (500 mL) extracted with ethyl acetate (3×300 mL) The combined organic extracts were then washed with a saturated aqueous sodium bicarbonate solution (1×150 mL) The organic layer was dried over magnesium sulfate filtered concentrated in vacuo

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

Procedure: reacting hydrogen sulfide with methyl acrylate in the presence of an ammonium hydroxide catalyst to give a mixture comprising methyl 3-mercaptopropionate and dimethyl thiodipropionate; and

Conditions: temp:25.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: A solution of dimethyl 3,3′-thiodipropionate (30.00 g, 144.0 mmol) in ethylene glycol dimethyl ether (200 mL), under nitrogen, was treated with sodium hydride (7.00 g, 145.8 mmol), and the reaction was heated under reflux for 1.5 h. The reaction mixture was then cooled to 25° C. and was slowly treated with a saturated aqueous sodium bicarbonate solution. The solvent was then removed in vacuo, and the resulting residue was diluted with water (500 mL) and extracted with ethyl acetate 3×300 mL). The combined organic extracts were then washed with a saturated aqueous sodium bicarbonate solution (1×150 mL) followed by a saturated aqueous sodium chloride solution (1×150 mL). The organic layer was dried over magnesium sulfate, filtered, and concentrated in vacuo. Biotage chromatography, performed in two batches, (FLASH 40M, Silica, 9/1 hexanes/diethyl ether) afforded 4-hydroxy-5,6-dihydro-2H-thiopyran-3-carboxylic acid methyl ester (12.89 g, 51.4%) as a colorless oil. the reaction was heated under reflux for 1.5 h The solvent was then removed in vacuo the resulting residue was diluted with water (500 mL) extracted with ethyl acetate 3×300 mL) The combined organic extracts were then washed with a saturated aqueous sodium bicarbonate solution (1×150 mL) The organic layer was dried over magnesium sulfate filtered concentrated in vacuo