(2,2-dimethyloxan-4-yl)methanol

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

Procedure: (2,2-Dimethyltetrahydro-2H-pyran-4-yl)methanol (2.54 g) was dissolved in dry DCM (40 mL) and triethylamine (4.9 mL) was added with stirring. The solution was cooled (ice bath) under nitrogen and methanesulphonyl chloride (1.77 mL) was added dropwise over 5 mins. The mixture was allowed to warm slowly to room temperature as the ice bath melted and was left for 16 h. The mixture was shaken with saturated sodium bicarbonate solution and the aqueous layer was extracted with DCM (×2). The combined organics were washed with brine, dried using a hydrophobic frit and evaporated to give the title compound (3.93 g). The solution was cooled (ice bath) under nitrogen the aqueous layer was extracted with DCM (×2) The combined organics were washed with brine dried evaporated

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

Procedure: (2,2-Dimethyltetrahydro-2H-pyran-4-yl)methanol (2.54 g) was dissolved in dry DCM (40 mL) and triethylamine (4.9 mL) was added with stirring. The solution was cooled (ice bath) under nitrogen and methanesulphonyl chloride (1.77 mL) was added dropwise over 5 mins. The mixture was allowed to warm slowly to room temperature as the ice bath melted and was left for 16 h. The mixture was shaken with saturated sodium bicarbonate solution and the aqueous layer was extracted with DCM (×2). The combined organics were washed with brine, dried using a hydrophobic frit and evaporated to give the title compound (3.93 g). The solution was cooled (ice bath) under nitrogen the aqueous layer was extracted with DCM (×2) The combined organics were washed with brine dried evaporated

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

Procedure: A solution of 2,2-dimethyltetrahydro-2H-pyran-4-carbaldehyde (2.5 g) in ethanol (30 mL) was cooled (ice bath) and sodium borohydride (665 mg) was added with stirring. The ice bath was removed and the mixture was allowed to warm to room temperature. After 2 h the reaction was heated to 50° C. for 1 h, then allowed to cool to room temperature. The solvent was evaporated and the residue was treated with brine, acidified and extracted into DCM (×3). The combined organics were dried through a hydrophobic frit and evaporated to give a clear oil (2.54 g). was added The ice bath was removed After 2 h the reaction was heated to 50° C. for 1 h to cool to room temperature The solvent was evaporated the residue was treated with brine extracted into DCM (×3) The combined organics were dried through a hydrophobic frit evaporated

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

Procedure: To a solution of (2,2-dimethyltetrahydro-2H-pyran-4-yl)methanol (2.50 g) in dichloromethane (30 mL) were added carbon tetrabromide (6.80 g) and triphenylphosphine (5.40 g), and the mixture was stirred at room temperature for 20 hr. Water was added and the mixture was extracted with diethyl ether. The extract was dried over anhydrous sodium sulfate and the solvent was evaporated under reduced pressure. The residue was purified by silica gel column chromatography (petroleum ether) to give the title compound (1.10 g) as a colorless oil. the mixture was extracted with diethyl ether The extract was dried over anhydrous sodium sulfate the solvent was evaporated under reduced pressure The residue was purified by silica gel column chromatography (petroleum ether)

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

Procedure: To a solution of (2,2-dimethyltetrahydro-2H-pyran-4-yl)methanol (2.50 g) in dichloromethane (30 mL) were added carbon tetrabromide (6.80 g) and triphenylphosphine (5.40 g), and the mixture was stirred at room temperature for 20 hr. Water was added and the mixture was extracted with diethyl ether. The extract was dried over anhydrous sodium sulfate and the solvent was evaporated under reduced pressure. The residue was purified by silica gel column chromatography (petroleum ether) to give the title compound (1.10 g) as a colorless oil. the mixture was extracted with diethyl ether The extract was dried over anhydrous sodium sulfate the solvent was evaporated under reduced pressure The residue was purified by silica gel column chromatography (petroleum ether)

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

Procedure: To a solution of 2,2-dimethyltetrahydro-2H-pyran-4-carbaldehyde (2.50 g) in methanol (15 mL) was slowly added at 0° C. sodium tetrahydroborate (3.30 g) by small portions, and the mixture was stirred at room temperature for 6 hr. The solvent was evaporated under reduced pressure, and saturated brine was added to the residue. The reaction mixture was extracted with dichloromethane, and the extract was dried over anhydrous sodium sulfate. The solvent was evaporated under reduced pressure to give the title compound (2.50 g) as a pale-yellow oil. This compound was used for the next step without further purification. The solvent was evaporated under reduced pressure, and saturated brine was added to the residue The reaction mixture was extracted with dichloromethane the extract was dried over anhydrous sodium sulfate The solvent was evaporated under reduced pressure

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

Procedure: To a solution of (2,2-dimethyltetrahydro-2H-pyran-4-yl)methanol (1 g, 6.93 mmol) in DCM (5 mL) and pyridine (5 mL, 61.8 mmol) was added para-toluenesulfonyl chloride (1.586 g, 8.32 mmol) and DMAP (0.042 g, 0.347 mmol). The mixture was stirred for 18 hr at ambient temperature. The reaction mixture was concentrated in vacuo and the resulting residue was diluted with water and DCM. The separated organic layer was washed with 0.2N aqueous HCl (1×), 1N aqueous HCl (2×), brine, dried over sodium sulfate, filtered off and concentrated in vacuo. The resulting residue was purified by column chromatography [SiO2, 40 g, EtOAc/hexane=0/100 to 50/50; 25 min] providing (R/S)-(2,2-dimethyltetrahydro-2H-pyran-4-yl)methyl 4-methylbenzenesulfonate as a colorless oil. Yield: 2.05 g. LCMS (m/z): 299.1 [M+H]+; Retention time=0.96 min. The reaction mixture was concentrated in vacuo the resulting residue was diluted with water and DCM The separated organic layer was washed with 0.2N aqueous HCl (1×), 1N aqueous HCl (2×), brine dried over sodium sulfate filtered off concentrated in vacuo The resulting residue was purified by column chromatography [SiO2, 40 g, EtOAc/hexane=0/100 to 50/50; 25 min]

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

Procedure: To a solution of (2,2-dimethyltetrahydro-2H-pyran-4-yl)methanol (1 g, 6.93 mmol) in DCM (5 mL) and pyridine (5 mL, 61.8 mmol) was added para-toluenesulfonyl chloride (1.586 g, 8.32 mmol) and DMAP (0.042 g, 0.347 mmol). The mixture was stirred for 18 hr at ambient temperature. The reaction mixture was concentrated in vacuo and the resulting resulting residue was diluted with water and DCM. The separated organic layer was washed with 0.2N aqueous HCl (1×), 1N aqueous HCl (2×), brine, dried over sodium sulfate, filtered off and concentrated in vacuo. The resulting residue was purified by column chromatography [SiO2, 40 g, EtOAc/hexane=0/100 to 50/50; 25 min] providing (R/S)-(2,2-dimethyltetrahydro-2H-pyran-4-yl)methyl 4-methylbenzenesulfonate as a colorless oil. Yield: 2.05 g. LCMS (m/z): 299.1 [M+H]+; Retention time=0.96 min. The reaction mixture was concentrated in vacuo the resulting resulting residue The separated organic layer was washed with 0.2N aqueous HCl (1×), 1N aqueous HCl (2×), brine dried over sodium sulfate filtered off concentrated in vacuo The resulting residue was purified by column chromatography [SiO2, 40 g, EtOAc/hexane=0/100 to 50/50; 25 min]

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

Procedure: (2,2-Dimethyltetrahydro-2H-pyran-4-yl)methanol (2.54 g) was dissolved in dry DCM (40 mL) and triethylamine (4.9 mL) was added with stirring. The solution was cooled (ice bath) under nitrogen and methanesulphonyl chloride (1.77 mL) was added dropwise over 5 mins. The mixture was allowed to warm slowly to room temperature as the ice bath melted and was left for 16 h. The mixture was shaken with saturated sodium bicarbonate solution and the aqueous layer was extracted with DCM (×2). The combined organics were washed with brine, dried using a hydrophobic frit and evaporated to give the title compound (3.93 g). The solution was cooled (ice bath) under nitrogen the aqueous layer was extracted with DCM (×2) The combined organics were washed with brine dried evaporated

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

Procedure: A solution of 2,2-dimethyltetrahydro-2H-pyran-4-carbaldehyde (2.5 g) in ethanol (30 mL) was cooled (ice bath) and sodium borohydride (665 mg) was added with stirring. The ice bath was removed and the mixture was allowed to warm to room temperature. After 2 h the reaction was heated to 50° C. for 1 h, then allowed to cool to room temperature. The solvent was evaporated and the residue was treated with brine, acidified and extracted into DCM (×3). The combined organics were dried through a hydrophobic frit and evaporated to give a clear oil (2.54 g). was added The ice bath was removed After 2 h the reaction was heated to 50° C. for 1 h to cool to room temperature The solvent was evaporated the residue was treated with brine extracted into DCM (×3) The combined organics were dried through a hydrophobic frit evaporated

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

Procedure: To a solution of (2,2-dimethyltetrahydro-2H-pyran-4-yl)methanol (2.50 g) in dichloromethane (30 mL) were added carbon tetrabromide (6.80 g) and triphenylphosphine (5.40 g), and the mixture was stirred at room temperature for 20 hr. Water was added and the mixture was extracted with diethyl ether. The extract was dried over anhydrous sodium sulfate and the solvent was evaporated under reduced pressure. The residue was purified by silica gel column chromatography (petroleum ether) to give the title compound (1.10 g) as a colorless oil. the mixture was extracted with diethyl ether The extract was dried over anhydrous sodium sulfate the solvent was evaporated under reduced pressure The residue was purified by silica gel column chromatography (petroleum ether)

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

Procedure: To a solution of 2,2-dimethyltetrahydro-2H-pyran-4-carbaldehyde (2.50 g) in methanol (15 mL) was slowly added at 0° C. sodium tetrahydroborate (3.30 g) by small portions, and the mixture was stirred at room temperature for 6 hr. The solvent was evaporated under reduced pressure, and saturated brine was added to the residue. The reaction mixture was extracted with dichloromethane, and the extract was dried over anhydrous sodium sulfate. The solvent was evaporated under reduced pressure to give the title compound (2.50 g) as a pale-yellow oil. This compound was used for the next step without further purification. The solvent was evaporated under reduced pressure, and saturated brine was added to the residue The reaction mixture was extracted with dichloromethane the extract was dried over anhydrous sodium sulfate The solvent was evaporated under reduced pressure