(5S)-5-(oxan-2-yloxymethyl)oxolan-2-one

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

Procedure: To a solution of (S)-5-(hydroxymethyl)dihydrofuran-2(3H)-one (1.0 g, 8.6 mmol, Acros) in dichloromethane (10 mL) were added 3,4-dihydro-2H-pyran (0.94 mL, 10.3 mmol, Aldrich) and pyridinium p-toluenesulfonate (0.22 g, 0.86 mmol, Aldrich). After stirring at room temperature overnight, the reaction mixture was washed with water (5 mL) and brine (5 mL). The organic extract was dried (Na2SO4), filtered, and concentrated. The residue was purified by column chromatography using an Analogix® Intelliflash280™ (SiO2, 0-100% ethyl acetate in hexanes) to obtain 1.6 g (93%) of the title compound. MS (DCI/NH3) m/z 218 (M+NH4)+. the reaction mixture was washed with water (5 mL) and brine (5 mL) The organic extract was dried (Na2SO4) filtered concentrated The residue was purified by column chromatography

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

Procedure: To a stirred solution of (S)-5-(hydroxymethyl)dihydrofuran-2(3H)-one (4.0 g, 34.45 mmol) in DCM (20 mL) was added 3,4-dihydro-2H-pyran (3.95 mL, 41.34 mmol) followed by pyridinium p-toluenesulfonate (0.86 g, 3.44 mmol) at room temperature and the mixture was stirred for 16 h. The reaction mixture was diluted with DCM (20 mL), quenched with water (40 mL) and extracted with DCM (2×50 mL). The combined organic layers were washed with brine (2×20 mL), dried over anhydrous Na2SO4, and concentrated under reduced pressure. The residue was purified by column chromatography (silica gel, 50% EtOAc/hexane as eluent) to provide compound A92-1 (5.85 mg, 85%) as a colorless gum. quenched with water (40 mL) extracted with DCM (2×50 mL) The combined organic layers were washed with brine (2×20 mL) dried over anhydrous Na2SO4 concentrated under reduced pressure The residue was purified by column chromatography (silica gel, 50% EtOAc/hexane as eluent) to provide compound A92-1 (5.85 mg, 85%) as a colorless gum

Conditions: temp:15.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: To a mixture of Ti(OiPr)4 (0.33 mL, 0.001 mol, Ardrich) and (5S)-5-((tetrahydro-2H-pyran-2-yloxy)methyl)-dihydrofuran-2(3H)-one (1.0 g, 0.005 mol) in 18.7 mL of THF was added a solution of 3M EtMgBr in Et2O (4.3 mL, 0.0125 mol, Aldrich) via a syringe over 3 hrs at 15° C. After stirring for additional one hour at 15° C., the reaction was quenched with 20 mL of saturated NH4Cl solution, filtered and extracted with EtOAc (50 mL×2). The combined organic phases were dried over Na2SO4 and concentrated in vacuo. The residue was purified by a silica gel column chromatography to afford 1-((S)-3-hydroxy-4-(tetrahydro-2H-pyran-2-yloxy)butyl)cyclopropanol as colorless oil (0.853 g, 74%)2. the reaction was quenched with 20 mL of saturated NH4Cl solution filtered extracted with EtOAc (50 mL×2) The combined organic phases were dried over Na2SO4 concentrated in vacuo The residue was purified by a silica gel column chromatography

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

Procedure: To a mixture of (S)-5-(hydroxymethyl)-dihydrofuran-2(3H)-one (1.78 g, 0.0153 mol) and 3,4-dihydro-2H-pyran (2.62 g, 0.0312 mol, Alfa) in 40 mL of CH2Cl2 was added PPTS (0.391 g, 0.00156 mol, Aldrich) slowly. After stirring at rt overnight, the reaction mixture was quenched with 5 mL of water. The mixture was extracted with EtOAc (50 mL×2). The combined organic phases were dried over Na2SO4 and concentrated in vacuo to give pale yellow oil. The crude product was purified by a silica gel column chromatography (3:1 (v/v) petroleum ether/EtOAc) to afford the title compound as colorless oil (2.7 g, 88%). the reaction mixture was quenched with 5 mL of water The mixture was extracted with EtOAc (50 mL×2) The combined organic phases were dried over Na2SO4 concentrated in vacuo to give pale yellow oil The crude product was purified by a silica gel column chromatography (3:1 (v/v) petroleum ether/EtOAc)

Conditions: temp:15.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: To a mixture of Ti(OiPr)4 (0.33 mL, 0.001 mol, Ardrich) and (5S)-5-((tetrahydro-2H-pyran-2-yloxy)methyl)-dihydrofuran-2(3H)-one (1.0 g, 0.005 mol) in 18.7 mL of THF was added a solution of 3M EtMgBr in Et2O (4.3 mL, 0.0125 mol, Aldrich) via a syringe over 3 hrs at 15° C. After stirring for additional one hour at 15° C., the reaction was quenched with 20 mL of saturated NH4Cl solution, filtered and extracted with EtOAc (50 mL×2). The combined organic phases were dried over Na2SO4 and concentrated in vacuo. The residue was purified by a silica gel column chromatography to afford 1-((S)-3-hydroxy-4-(tetrahydro-2H-pyran-2-yloxy)butyl)cyclopropanol as colorless oil (0.853 g, 74%)2. the reaction was quenched with 20 mL of saturated NH4Cl solution filtered extracted with EtOAc (50 mL×2) The combined organic phases were dried over Na2SO4 concentrated in vacuo The residue was purified by a silica gel column chromatography

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

Procedure: To a mixture of (S)-5-(hydroxymethyl)-dihydrofuran-2(3H)-one (1.78 g, 0.0153 mol) and 3,4-dihydro-2H-pyran (2.62 g, 0.0312 mol, Alfa) in 40 mL of CH2Cl2 was added PPTS (0.391 g, 0.00156 mol, Aldrich) slowly. After stirring at rt overnight, the reaction mixture was quenched with 5 mL of water. The mixture was extracted with EtOAc (50 mL×2). The combined organic phases were dried over Na2SO4 and concentrated in vacuo to give pale yellow oil. The crude product was purified by a silica gel column chromatography (3:1 (v/v) petroleum ether/EtOAc) to afford the title compound as colorless oil (2.7 g, 88%). the reaction mixture was quenched with 5 mL of water The mixture was extracted with EtOAc (50 mL×2) The combined organic phases were dried over Na2SO4 concentrated in vacuo to give pale yellow oil The crude product was purified by a silica gel column chromatography (3:1 (v/v) petroleum ether/EtOAc)

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

Procedure: To a solution of (S)-5-(hydroxymethyl)dihydrofuran-2(3H)-one (1.0 g, 8.6 mmol, Acros) in dichloromethane (10 mL) were added 3,4-dihydro-2H-pyran (0.94 mL, 10.3 mmol, Aldrich) and pyridinium p-toluenesulfonate (0.22 g, 0.86 mmol, Aldrich). After stirring at room temperature overnight, the reaction mixture was washed with water (5 mL) and brine (5 mL). The organic extract was dried (Na2SO4), filtered, and concentrated. The residue was purified by column chromatography using an Analogix® Intelliflash280™ (SiO2, 0-100% ethyl acetate in hexanes) to obtain 1.6 g (93%) of the title compound. MS (DCI/NH3) m/z 218 (M+NH4)+. the reaction mixture was washed with water (5 mL) and brine (5 mL) The organic extract was dried (Na2SO4) filtered concentrated The residue was purified by column chromatography

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

Procedure: To a solution of (S)-5-(hydroxymethyl)dihydrofuran-2(3H)-one (1.0 g, 8.6 mmol, Acros) in dichloromethane (10 mL) were added 3,4-dihydro-2H-pyran (0.94 mL, 10.3 mmol, Aldrich) and pyridinium p-toluenesulfonate (0.22 g, 0.86 mmol, Aldrich). After stirring at room temperature overnight, the reaction mixture was washed with water (5 mL) and brine (5 mL). The organic extract was dried (Na2SO4), filtered, and concentrated. The residue was purified by column chromatography using an Analogix® Intelliflash280™ (SiO2, 0-100% ethyl acetate in hexanes) to obtain 1.6 g (93%) of the title compound. MS (DCI/NH3) m/z 218 (M+NH4)+. the reaction mixture was washed with water (5 mL) and brine (5 mL) The organic extract was dried (Na2SO4) filtered concentrated The residue was purified by column chromatography