ethyl 4-oxooxane-2-carboxylate

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: A mixture of 4-oxo-3,4-dihydro-2H-pyran-2-carboxylic acid ethyl ester (8.0 g, 46 mmol) and Pd/C (10%, 0.20 g) in ethyl acetate (70 mL) was stirred under hydrogen (1 atm) for 4 hours. The mixture was filtered through a pad of Celite®. The filtrate was concentrated, and the residue was purified by silica gel column using 30% EtOAc in petroleum ether to give 4-oxo-tetrahydro-pyran-2-carboxylic acid ethyl ester (2.62 g, 33% yield) as an oil. 1H NMR (500 MHz, CDCl3) δ 4.40 (m, 1H), 4.23-4.31 (m, 3H), 3.79 (m, 1H), 2.61-2.74 (m, 3H), 2.40 (d, J=15.0 Hz, 1H), 1.31 (t, J=7.5 Hz, 3H). The mixture was filtered through a pad of Celite® The filtrate was concentrated the residue was purified by silica gel column

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

Procedure: A mixture of 4-oxo-3,4-dihydro-2H-pyran-2-carboxylic acid ethyl ester (8.0 g, 46 mmol) and Pd/C (10%, 0.20 g) in ethyl acetate (70 mL) was stirred under hydrogen (1 atm) for 4 hours. The mixture was filtered through a pad of Celite®. The filtrate was concentrated, and the residue was purified by silica gel column using 30% EtOAc in petroleum ether to give 4-oxo-tetrahydro-pyran-2-carboxylic acid ethyl ester (2.62 g, 33% yield) as an oil. 1H NMR (500 MHz, CDCl3) δ 4.40 (m, 1H), 4.23-4.31 (m, 3H), 3.79 (m, 1H), 2.61-2.74 (m, 3H), 2.40 (d, J=15.0 Hz, 1H), 1.31 (t, J=7.5 Hz, 3H). The mixture was filtered through a pad of Celite® The filtrate was concentrated the residue was purified by silica gel column

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

Procedure: To a cooled (0° C.), stirred suspension of LiAlH4 (3.42 g, 90.0 mmol) in anhydrous THF (50 mL) was added dropwise a solution of 4-oxo-tetrahydro-pyran-2-carboxylic acid ethyl ester (5.17 g, 30.0 mmol). After stirring for 1 hour, the reaction was quenched by the slow, sequential addition of water (3.4 mL), 15% NaOH (3.4 mL), and water (10.0 mL). The inorganic salt was filtered off and extracted with EtOAc repeatedly since the product was absorbed on the solid. Solvent removal afforded 2.42 g (61%) of yellow oil. The crude mixture was carried to the next step without purification. After stirring for 1 hour the reaction was quenched by the slow, sequential addition of water (3.4 mL), 15% NaOH (3.4 mL), and water (10.0 mL) The inorganic salt was filtered off extracted with EtOAc repeatedly since the product was absorbed on the solid Solvent removal

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

Procedure: A mixture of 4-oxo-3,4-dihydro-2H-pyran-2-carboxylic acid ethyl ester (8.0 g, 46.0 mmol) and Pd/C (10%, 0.20 g) in EtOAc (70 mL) was shaken in a Parr bottle with hydrogen at 50 psi overnight and filtered through a pad of Celite. The filtrate was concentrated and the residue was distilled to give 2.62 g (33%) of yellowish oil: 1H NMR (CDCl3) δ 1.29 (t, 3H), 2.40 (d, 1H), 2.58-2.75 (m 3H), 3.79 (tt, 1H), 4.23 (q, 2H), 4.28 (m 1H), 4.40 (m, 1H). filtered through a pad of Celite The filtrate was concentrated the residue was distilled

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

Procedure: To a cooled (0° C.), stirred suspension of LiAlH4 (3.42 g, 90.0 mmol) in anhydrous THF (50 mL) was added dropwise a solution of 4-oxo-tetrahydro-pyran-2-carboxylic acid ethyl ester (5.17 g, 30.0 mmol). After stirring for 1 hour, the reaction was quenched by the slow, sequential addition of water (3.4 mL), 15% NaOH (3.4 mL), and water (10.0 mL). The inorganic salt was filtered off and extracted with EtOAc repeatedly since the product was absorbed on the solid. Solvent removal afforded 2.42 g (61%) of yellow oil. The crude mixture was carried to the next step without purification. After stirring for 1 hour the reaction was quenched by the slow, sequential addition of water (3.4 mL), 15% NaOH (3.4 mL), and water (10.0 mL) The inorganic salt was filtered off extracted with EtOAc repeatedly since the product was absorbed on the solid Solvent removal

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

Procedure: A cold (−78° C.), stirred solution of (trimethylsilyl)acetylene (1.80 g, 18.24 mmol) in anhydrous THF (30 mL) was treated with nBuLi (7.3 mL in hexane, 18.24 mmol) under nitrogen. The colorless solution was stirred for 30 minutes and followed by the addition of 4-oxo-tetrahydro-pyran-2-carboxylic acid ethyl ester (2.62 g, 15.2 mmol) in anhydrous THF (30 mL). The reaction was warmed up to room temperature, stirred for 2 hours, and quenched with water (30 mL). After removal of THF, the product was extracted with EtOAc (2×60 mL). The combined organic layer was washed with brine, dried over sodium sulfate, and concentrated to give 2.50 g (61%) of yellow oil: 1H NMR (CDCl3) δ 0.17 (s, 9H), 1.30 (t, 3H), 1.76-1.90 (m, 3H), 2.25 (m, 1H), 3.66 (tt, 1H), 4.11-4.21 (m, 2H), 4.24 (q, 2H). stirred for 2 hours quenched with water (30 mL) After removal of THF the product was extracted with EtOAc (2×60 mL) The combined organic layer was washed with brine dried over sodium sulfate concentrated

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

Procedure: A mixture of 4-oxo-3,4-dihydro-2H-pyran-2-carboxylic acid ethyl ester (8.0 g, 46.0 mmol) and PdlC (10%, 0.20 g,) in EtOAc (70 mL) was shaken in a Parr bottle with hydrogen at 50 psi overnight and filtered through a pad of Celite. The filtrate was concentrated and the residue was distilled to give 2.62 g (33%) of yellowish oil: 1H NMR (CDCl3) δ 1.29 (t, 3H), 2.40 (d, 1H), 2.58-2.75 (m 3H), 3.79 (tt, 1H), 4.23 (q, 2H), 4.28 (m 1H), 4.40 (m, 1H). filtered through a pad of Celite The filtrate was concentrated the residue was distilled

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