4-(2-trimethylsilylethynyl)oxan-4-ol

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

Procedure: To a cooled solution (0° C.) of 4-{(trimethylsilyl)ethynyl}tetrahydropyran-4-ol prepared as described in the above example (2.5 g, 12.6 mmol) in a THF-DMF mixture (55 mL, 10:1), sodium hydride (60% suspension in oil, 0.504 g, 12.6 mmol) was added portionwise. After addition, the mixture was stirred 15 minutes before iodomethane (0.788 mL, 12.6 mmol) was added. The temperature was slowly raised to room temperature and the reaction was stirred for another 2 hours. The reaction mixture was then quenched with water and the product was extracted with ethyl acetate (2×). The combined organic layers were diluted with hexanes and washed with water and brine, dried over MgSO4, filtered and concentrated. The crude residue obtained was purified by column chromatography (acetone/dichloromethane, 2:98) to afford the title compound. 1H NMR (400 MHz, acetone-d6): 3.82-3.74 (m, 2H), 3.61-3.54 (m, 2H), 3.34 (s, 3H), 1.90-1.82 (m, 2H), 1.71-1.63 (m, 2H), 0.21 (s, 9H). was added portionwise After addition was added The reaction mixture was then quenched with water the product was extracted with ethyl acetate (2×) The combined organic layers were diluted with hexanes washed with water and brine dried over MgSO4 filtered concentrated The crude residue obtained was purified by column chromatography (acetone/dichloromethane, 2:98)

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

Procedure: To a cooled solution (0° C.) of 4-{(trimethylsilyl)ethynyl}tetrahydropyran-4-ol prepared as described in the above example (2.5 g, 12.6 mmol) in a THF-DMF mixture (55 mL, 10:1), sodium hydride (60% suspension in oil, 0.504 g, 12.6 mmol) was added portionwise. After addition, the mixture was stirred 15 minutes before iodomethane (0.788 mL, 12.6 mmol) was added. The temperature was slowly raised to room temperature and the reaction was stirred for another 2 hours. The reaction mixture was then quenched with water and the product was extracted with ethyl acetate (2×). The combined organic layers were diluted with hexanes and washed with water and brine, dried over MgSO4, filtered and concentrated. The crude residue obtained was purified by column chromatography (acetone/dichloromethane, 2:98) to afford the title compound. 1H NMR (400 MHz, acetone-d6): 3.82-3.74 (m, 2H), 3.61-3.54 (m, 2H), 3.34 (s, 3H), 1.90-1.82 (m, 2H), 1.71-1.63 (m, 2H), 0.21 (s, 9H). was added portionwise After addition was added The reaction mixture was then quenched with water the product was extracted with ethyl acetate (2×) The combined organic layers were diluted with hexanes washed with water and brine dried over MgSO4 filtered concentrated The crude residue obtained was purified by column chromatography (acetone/dichloromethane, 2:98)

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

Procedure: To a cooled solution (0° C.) of 4-{(trimethylsilyl)ethynyl}tetrahydropyran-4-ol prepared as described in the above example (2.5 g, 12.6 mmol) in a THF-DMF mixture (55 mL, 10:1), sodium hydride (60% suspension in oil, 0.504 g, 12.6 mmol) was added portionwise. After addition, the mixture was stirred 15 minutes before iodomethane (0.788 mL, 12.6 mmol) was added. The temperature was slowly raised to room temperature and the reaction was stirred for another 2 hours. The reaction mixture was then quenched with water and the product was extracted with ethyl acetate (2×). The combined organic layers were diluted with hexanes and washed with water and brine, dried over MgSO4, filtered and concentrated. The crude residue obtained was purified by column chromatography (acetone/dichloromethane, 2:98) to afford the title compound. 1H NMR (400 MHz, acetone-d6): 3.82-3.74 (m, 2H), 3.61-3.54 (m, 2H), 3.34 (s, 3H), 1.90-1.82 (m, 2H), 1.71-1.63 (m, 2H), 0.21 (s, 9H). was added portionwise After addition was added The reaction mixture was then quenched with water the product was extracted with ethyl acetate (2×) The combined organic layers were diluted with hexanes washed with water and brine dried over MgSO4 filtered concentrated The crude residue obtained was purified by column chromatography (acetone/dichloromethane, 2:98)

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

Procedure: To a solution of 4-{(trimethylsilyl)ethynyl}tetrahydropyran-4-ol (1.0 g, 5.04 mmol) in THF (SnL), a 1 M solution of tetrabutyl ammonium fluoride in THF (5.29 mL, 5.29 mmol) was added and the reaction was stirred 2 hours at room temperature. The reaction mixture was then poured into an aqueous 5% NH4OAc solution and diluted with ethyl acetate. The isolated organic layer was washed with brine, dried over MgSO4, filtered and concentrated. The crude residue obtained was used as such for the next step. 1H NMR (400 MHz, acetone-d6): 4.61 (s, 1H), 3.87-3.77 (m, 2H), 3.60-3.50 (m, 2H), 2.98 (s, 1H), 1.89-1.81 (m, 2H), 1.77-1.65 (m, 2H). The isolated organic layer was washed with brine dried over MgSO4 filtered concentrated

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

Procedure: To a solution of trimethylsilylacetylene (5 mL, 35.4 mmol) in THF (100 mL) cooled at −78° C., a 1.6M n-butyllithium in hexanes (22.1 mL, 35.4 mmol) was added dropwise. The solution was stirred for 30 min before tetrahydro-4H-pyran-4-one (3.47 mL, 37.2 mmol) was added. The temperature was slowly raised to room temperature and the reaction was stirred overnight. The reaction was quenched with a saturated ammonium chloride solution and the aqueous layer was extracted with ethyl acetate (3×). The combined organic layers were washed with brine, dried over MgSO4, filtered and concentrated under reduced pressure. The crude residue obtained was used as such for the next step. 1H NMR (400 MHz, acetone-d6): 4.60 (s, 1H), 3.85-3.75 (m, 2H), 3.61-3.51 (m, 2H), 1.98-1.87 (m, 2H), 1.74-1.66 (m, 2H), 0.16 (s, 9H). was added The reaction was quenched with a saturated ammonium chloride solution the aqueous layer was extracted with ethyl acetate (3×) The combined organic layers were washed with brine dried over MgSO4 filtered concentrated under reduced pressure

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

Procedure: To a solution of trimethylsilylacetylene (5 mL, 35.4 mmol) in THF (100 mL) cooled at −78° C., a 1.6M n-butyllithium in hexanes (22.1 mL, 35.4 mmol) was added dropwise. The solution was stirred for 30 min before tetrahydro-4H-pyran-4-one (3.47 mL, 37.2 mmol) was added. The temperature was slowly raised to room temperature and the reaction was stirred overnight. The reaction was quenched with a saturated ammonium chloride solution and the aqueous layer was extracted with ethyl acetate (3×). The combined organic layers were washed with brine, dried over MgSO4, filtered and concentrated under reduced pressure. The crude residue obtained was used as such for the next step. 1H NMR (400 MHz, acetone-d6): 4.60 (s, 1H), 3.85-3.75 (m, 2H), 3.61-3.51 (m, 2H), 1.98-1.87 (m, 2H), 1.74-1.66 (m, 2H), 0.16 (s, 9H). was added The reaction was quenched with a saturated ammonium chloride solution the aqueous layer was extracted with ethyl acetate (3×) The combined organic layers were washed with brine dried over MgSO4 filtered concentrated under reduced pressure