6-methoxyoxan-3-ol

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

Procedure: At 0° C. to a solution of 6-methoxytetrahydro-2H-pyran-3-ol (222 mg, 1.680 mmol) in DMF (2 mL) was added 60% NaH (81 mg, 2.02 mmol) and the mixture was allowed to warm to rt and stirred at rt for 30 min. A solution of (bromomethyl)benzene (345 mg, 2.016 mmol) in DMF (1 ml) was added and the mixture was stirred at rt for 18 h. The reaction mixture was diluted with ether and quenched with water. The crude product was purified by silica gel FCC (20% EtOAc in hexanes) to afford 5-(benzyloxy)-2-methoxytetrahydro-2H-pyran. 1H NMR (400 MHz, CDCl3) δ ppm 7.29-7.41 (5H, m), 4.53-4.64 (3H, m), 3.90 (1H, dd, J=12.05, 2.51 Hz), 3.56-3.65 (1H, m), 3.46-3.53 (1H, m), 3.43 (3H, s), 1.97-2.14 (2H, m), 1.69-1.81 (1H, m), 1.48-1.60 (1H, m). the mixture was stirred at rt for 18 h quenched with water The crude product was purified by silica gel FCC (20% EtOAc in hexanes)

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

Procedure: PDC (6.0 g, 28 mmol) was added to a solution of 6-methoxytetrahydro-2H-pyran-3-ol (2.0 g, 15 mmol) from step (394a) in methylene chloride (50 ml) at room temperature. The reaction was stirred overnight, filtered through silica gel and concentrated to give an oil. The product was distilled at 35° C. at 1000 mtorr pressure to give the 6-methoxydihydro-2H-pyran-3-(4H)-one (0.5 g, 25%) as an oil. filtered through silica gel concentrated to give an oil The product was distilled at 35° C. at 1000 mtorr pressure

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

Procedure: Borane-THF 1M (14.6 ml, 14.6 mmol) was added slowly to an ice cooled solution of 3,4-dihydro-2-methoxy-2H-pyran (55.0 g, 44 mmol) in THF (15 ml). The ice bath was removed and the reaction was stirred at room temperature for 1 h, cooled to 0° C. and 3 N sodium hydroxide (14.6 ml) was added followed with 30% hydrogen peroxide (9 ml). This was allowed to stir for 4 hs warming to room temperature. The reaction was extracted with ethyl acetate (2×50 ml). The combined organic layer was washed with brine, dried over magnesium sulfate and concentrated to give 6-methoxytetrahydro-2H-pyran-3-ol (4.2 g, 72%) as an oil. The ice bath was removed cooled to 0° C. 3 N sodium hydroxide (14.6 ml) was added to stir for 4 hs warming to room temperature The reaction was extracted with ethyl acetate (2×50 ml) The combined organic layer was washed with brine dried over magnesium sulfate concentrated

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

Procedure: Borane-THF 1M (14.6 ml, 14.6 mmol) was added slowly to an ice cooled solution of 3,4-dihydro-2-methoxy-2H-pyran (55.0 g, 44 mmol) in THF (15 ml). The ice bath was removed and the reaction was stirred at room temperature for 1 h, cooled to 0° C. and 3 N sodium hydroxide (14.6 ml) was added followed with 30% hydrogen peroxide (9 ml). This was allowed to stir for 4 hs warming to room temperature. The reaction was extracted with ethyl acetate (2×50 ml). The combined organic layer was washed with brine, dried over magnesium sulfate and concentrated to give 6-methoxytetrahydro-2H-pyran-3-ol (4.2 g, 72%) as an oil. The ice bath was removed cooled to 0° C. 3 N sodium hydroxide (14.6 ml) was added to stir for 4 hs warming to room temperature The reaction was extracted with ethyl acetate (2×50 ml) The combined organic layer was washed with brine dried over magnesium sulfate concentrated

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

Procedure: At 0° C. to a solution of 6-methoxytetrahydro-2H-pyran-3-ol (222 mg, 1.680 mmol) in DMF (2 mL) was added 60% NaH (81 mg, 2.02 mmol) and the mixture was allowed to warm to rt and stirred at rt for 30 min. A solution of (bromomethyl)benzene (345 mg, 2.016 mmol) in DMF (1 ml) was added and the mixture was stirred at rt for 18 h. The reaction mixture was diluted with ether and quenched with water. The crude product was purified by silica gel FCC (20% EtOAc in hexanes) to afford 5-(benzyloxy)-2-methoxytetrahydro-2H-pyran. 1H NMR (400 MHz, CDCl3) δ ppm 7.29-7.41 (5H, m), 4.53-4.64 (3H, m), 3.90 (1H, dd, J=12.05, 2.51 Hz), 3.56-3.65 (1H, m), 3.46-3.53 (1H, m), 3.43 (3H, s), 1.97-2.14 (2H, m), 1.69-1.81 (1H, m), 1.48-1.60 (1H, m). the mixture was stirred at rt for 18 h quenched with water The crude product was purified by silica gel FCC (20% EtOAc in hexanes)