methyl 2-(5-hydroxyoxan-2-yl)-2-methylpropanoate

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

Procedure: To a stirred solution of methyl 2-(5-hydroxytetrahydro-2H-pyran-2-yl)-2-methylpropanoate (187 mg, 0.925 mmol) in DCM (5 mL) containing 4 Å molecular seives (˜250 mg) was added PCC (259 mg, 1.202 mmol). The reaction mixture was stirred at rt for 3 h, then loaded onto a silica gel column and eluted with 10-20% EtOAc in DCM to afford methyl 2-methyl-2-(5-oxotetrahydro-2H-pyran-2-yl)propanoate as a clear oil (105 mg). 1H NMR (400 MHz, CDCl3) δ ppm 4.18 (1H, dd, J=16.56, 1.76 Hz), 3.87-4.01 (2H, m), 3.73 (3H, s), 2.59-2.69 (1H, m), 2.48 (1H, dt, J=17.13, 8.63 Hz), 1.93-2.04 (2H, m), 1.27 (3H, s), 1.15-1.24 (3H, m). eluted with 10-20% EtOAc in DCM

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

Procedure: To a solution of 5-(benzyloxy)tetrahydro-2H-pyran-2-yl acetate (281 mg, 1.123 mmol) and ((1-methoxy-2-methylprop-1-en-1-yl)oxy)trimethylsilane (783 mg, 4.49 mmol) in DCM (5 mL) at −78° C. was added BF3.OEt2 (0.228 mL, 1.796 mmol). The reaction mixture was gradually allowed to warm to rt and stirred at rt for 18 h. The reaction mixture was quenched with sat. NaHCO3 (5 mL) and diluted with DCM (20 mL). The organic layer was separated, washed with water, brine, dried (MgSO4) and concentrated. The crude product was purified by silica gel FCC (10-20% EtOAc in hexanes) to afford methyl 2-(5-(benzyloxy)tetrahydro-2H-pyran-2-yl)-2-methylpropanoate as a colorless oil (253 mg). To a solution of methyl 2-(5-(benzyloxy)tetrahydro-2H-pyran-2-yl)-2-methylpropanoate (250 mg) in MeOH (20 mL) was added 10% Pd—C (59.7 mg) and the reaction mixture was hydrogenated at 40 psi overnight. The suspension was filtered and the filtrate was evaporated to dryness to afford methyl 2-(5-hydroxytetrahydro-2H-pyran-2-yl)-2-methylpropanoate as a clear oil (188 mg). was hydrogenated at 40 psi overnight The suspension was filtered the filtrate was evaporated to dryness

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

Procedure: To a solution of 5-(benzyloxy)tetrahydro-2H-pyran-2-yl acetate (281 mg, 1.123 mmol) and ((1-methoxy-2-methylprop-1-en-1-yl)oxy)trimethylsilane (783 mg, 4.49 mmol) in DCM (5 mL) at −78° C. was added BF3.OEt2 (0.228 mL, 1.796 mmol). The reaction mixture was gradually allowed to warm to rt and stirred at rt for 18 h. The reaction mixture was quenched with sat. NaHCO3 (5 mL) and diluted with DCM (20 mL). The organic layer was separated, washed with water, brine, dried (MgSO4) and concentrated. The crude product was purified by silica gel FCC (10-20% EtOAc in hexanes) to afford methyl 2-(5-(benzyloxy)tetrahydro-2H-pyran-2-yl)-2-methylpropanoate as a colorless oil (253 mg). To a solution of methyl 2-(5-(benzyloxy)tetrahydro-2H-pyran-2-yl)-2-methylpropanoate (250 mg) in MeOH (20 mL) was added 10% Pd—C (59.7 mg) and the reaction mixture was hydrogenated at 40 psi overnight. The suspension was filtered and the filtrate was evaporated to dryness to afford methyl 2-(5-hydroxytetrahydro-2H-pyran-2-yl)-2-methylpropanoate as a clear oil (188 mg). was hydrogenated at 40 psi overnight The suspension was filtered the filtrate was evaporated to dryness

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

Procedure: To a stirred solution of methyl 2-(5-hydroxytetrahydro-2H-pyran-2-yl)-2-methylpropanoate (187 mg, 0.925 mmol) in DCM (5 mL) containing 4 Å molecular seives (˜250 mg) was added PCC (259 mg, 1.202 mmol). The reaction mixture was stirred at rt for 3 h, then loaded onto a silica gel column and eluted with 10-20% EtOAc in DCM to afford methyl 2-methyl-2-(5-oxotetrahydro-2H-pyran-2-yl)propanoate as a clear oil (105 mg). 1H NMR (400 MHz, CDCl3) δ ppm 4.18 (1H, dd, J=16.56, 1.76 Hz), 3.87-4.01 (2H, m), 3.73 (3H, s), 2.59-2.69 (1H, m), 2.48 (1H, dt, J=17.13, 8.63 Hz), 1.93-2.04 (2H, m), 1.27 (3H, s), 1.15-1.24 (3H, m). eluted with 10-20% EtOAc in DCM

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

Procedure: To a solution of 5-(benzyloxy)tetrahydro-2H-pyran-2-yl acetate (281 mg, 1.123 mmol) and ((1-methoxy-2-methylprop-1-en-1-yl)oxy)trimethylsilane (783 mg, 4.49 mmol) in DCM (5 mL) at −78° C. was added BF3.OEt2 (0.228 mL, 1.796 mmol). The reaction mixture was gradually allowed to warm to rt and stirred at rt for 18 h. The reaction mixture was quenched with sat. NaHCO3 (5 mL) and diluted with DCM (20 mL). The organic layer was separated, washed with water, brine, dried (MgSO4) and concentrated. The crude product was purified by silica gel FCC (10-20% EtOAc in hexanes) to afford methyl 2-(5-(benzyloxy)tetrahydro-2H-pyran-2-yl)-2-methylpropanoate as a colorless oil (253 mg). To a solution of methyl 2-(5-(benzyloxy)tetrahydro-2H-pyran-2-yl)-2-methylpropanoate (250 mg) in MeOH (20 mL) was added 10% Pd—C (59.7 mg) and the reaction mixture was hydrogenated at 40 psi overnight. The suspension was filtered and the filtrate was evaporated to dryness to afford methyl 2-(5-hydroxytetrahydro-2H-pyran-2-yl)-2-methylpropanoate as a clear oil (188 mg). was hydrogenated at 40 psi overnight The suspension was filtered the filtrate was evaporated to dryness