2-(3-chloropropyl)oxolane

Conditions: temp:140.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: To a mixture of 2-fluoro-4-nitroaniline (7.02 g, 45.0 mmol), Cs2CO3 (29.3 g, 90.0 mmol), KI (16.6 g, 100 mmol) and DMF (100 mL) was added 2-(3-chloropropyl)tetrahydrofuran (7.43 g, 50.0 mmol) dropwise under N2 and the mixture was stirred at 140° C. for 48 h. The mixture was cooled to rt and filtered and the filtrate was concentrated in vacuo. To the residue was added water (30 mL) and the mixture was extracted with DCM (30 mL×4). The combined organic layers were washed with brine (40 mL×2), dried over anhydrous Na2SO4 and concentrated in vacuo. The residue was purified by a silica gel column chromatography (PE/EtOAc (V/V)=20:1) to give the title compound as a yellow solid (3.74 g, 31%). The mixture was cooled to rt filtered the filtrate was concentrated in vacuo To the residue was added water (30 mL) the mixture was extracted with DCM (30 mL×4) The combined organic layers were washed with brine (40 mL×2) dried over anhydrous Na2SO4 concentrated in vacuo The residue was purified by a silica gel column chromatography (PE/EtOAc (V/V)=20:1)

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

Procedure: To 3-(tetrahydrofuran-2-yl)propan-1-ol (3.90 g, 30.0 mmol) was added dichlorosulfoxide (15 mL) dropwise under N2 and the mixture was refluxed for 3.5 h. It was then cooled to rt and concentrated in vacuo. To the residue was added water (30 mL) and the resulting mixture was extracted with DCM (30 mL×4). The combined organic layers were washed with brine (40 mL×2), dried over anhydrous Na2SO4 and concentrated in vacuo to give the title compound as yellow liquid, which was used for next step without further purification. the mixture was refluxed for 3.5 h concentrated in vacuo To the residue was added water (30 mL) the resulting mixture was extracted with DCM (30 mL×4) The combined organic layers were washed with brine (40 mL×2) dried over anhydrous Na2SO4 concentrated in vacuo

Conditions: temp:140.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: To a mixture of 2-fluoro-4-nitroaniline (7.02 g, 45.0 mmol), Cs2CO3 (29.3 g, 90.0 mmol), KI (16.6 g, 100 mmol) and DMF (100 mL) was added 2-(3-chloropropyl)tetrahydrofuran (7.43 g, 50.0 mmol) dropwise under N2 and the mixture was stirred at 140° C. for 48 h. The mixture was cooled to rt and filtered and the filtrate was concentrated in vacuo. To the residue was added water (30 mL) and the mixture was extracted with DCM (30 mL×4). The combined organic layers were washed with brine (40 mL×2), dried over anhydrous Na2SO4 and concentrated in vacuo. The residue was purified by a silica gel column chromatography (PE/EtOAc (V/V)=20:1) to give the title compound as a yellow solid (3.74 g, 31%). The mixture was cooled to rt filtered the filtrate was concentrated in vacuo To the residue was added water (30 mL) the mixture was extracted with DCM (30 mL×4) The combined organic layers were washed with brine (40 mL×2) dried over anhydrous Na2SO4 concentrated in vacuo The residue was purified by a silica gel column chromatography (PE/EtOAc (V/V)=20:1)

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

Procedure: To 3-(tetrahydrofuran-2-yl)propan-1-ol (3.90 g, 30.0 mmol) was added dichlorosulfoxide (15 mL) dropwise under N2 and the mixture was refluxed for 3.5 h. It was then cooled to rt and concentrated in vacuo. To the residue was added water (30 mL) and the resulting mixture was extracted with DCM (30 mL×4). The combined organic layers were washed with brine (40 mL×2), dried over anhydrous Na2SO4 and concentrated in vacuo to give the title compound as yellow liquid, which was used for next step without further purification. the mixture was refluxed for 3.5 h concentrated in vacuo To the residue was added water (30 mL) the resulting mixture was extracted with DCM (30 mL×4) The combined organic layers were washed with brine (40 mL×2) dried over anhydrous Na2SO4 concentrated in vacuo

Conditions: temp:140.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: To a mixture of 2-fluoro-4-nitroaniline (7.02 g, 45.0 mmol), Cs2CO3 (29.3 g, 90.0 mmol), KI (16.6 g, 100 mmol) and DMF (100 mL) was added 2-(3-chloropropyl)tetrahydrofuran (7.43 g, 50.0 mmol) dropwise under N2 and the mixture was stirred at 140° C. for 48 h. The mixture was cooled to rt and filtered and the filtrate was concentrated in vacuo. To the residue was added water (30 mL) and the mixture was extracted with DCM (30 mL×4). The combined organic layers were washed with brine (40 mL×2), dried over anhydrous Na2SO4 and concentrated in vacuo. The residue was purified by a silica gel column chromatography (PE/EtOAc (V/V)=20:1) to give the title compound as a yellow solid (3.74 g, 31%). The mixture was cooled to rt filtered the filtrate was concentrated in vacuo To the residue was added water (30 mL) the mixture was extracted with DCM (30 mL×4) The combined organic layers were washed with brine (40 mL×2) dried over anhydrous Na2SO4 concentrated in vacuo The residue was purified by a silica gel column chromatography (PE/EtOAc (V/V)=20:1)

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

Procedure: To 3-(tetrahydrofuran-2-yl)propan-1-ol (3.90 g, 30.0 mmol) was added dichlorosulfoxide (15 mL) dropwise under N2 and the mixture was refluxed for 3.5 h. It was then cooled to rt and concentrated in vacuo. To the residue was added water (30 mL) and the resulting mixture was extracted with DCM (30 mL×4). The combined organic layers were washed with brine (40 mL×2), dried over anhydrous Na2SO4 and concentrated in vacuo to give the title compound as yellow liquid, which was used for next step without further purification. the mixture was refluxed for 3.5 h concentrated in vacuo To the residue was added water (30 mL) the resulting mixture was extracted with DCM (30 mL×4) The combined organic layers were washed with brine (40 mL×2) dried over anhydrous Na2SO4 concentrated in vacuo