3-(oxan-4-yl)propanal

Conditions: temp:0.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: To a stirred solution of 3-(tetrahydro-pyran-4-yl)-propionaldehyde (8.59 g, 0.06 mol) and dibenzyl azodicarboxylate (12.8 g, 0.042 mol) in MeCN (250 mL) at 0° C. was added (R-proline) (0.48 g, 0.0042 mol). After stirring the mixture at 0° C. for 15 h, ethanol (100 mL) and NaBH4 (1.56 g, 0.042 mol) were added, and the mixture was stirred at 0° C. for 40 min. The reaction was quenched by slow addition of 10% aq citric acid (15 mL), and the whole solution was concentrated in vacuo. This residue was diluted with EtOAc (200 mL), washed with brine (50 mL), dried over Na2SO4, and concentrated in vacuo to give crude product which was purified by column chromatography to give (S)-dibenzyl 1-(1-hydroxy-3-(tetrahydro-2H-pyran-4-yl)propan-2-yl)hydrazine-1,2-dicarboxylate (16.52 g, 89%). 1H NMR (CD3OD) δ 1.0-1.5 (m, 8H), 2.9-3.3 (m, 2H), 3.4-3.6 (m, 2H), 3.7-3.9 (m, 2H), 4.4-4.7 (m, 2H), 5.1-5.4 (m, 4H), 7.2-7.4 (m, 10H). the mixture was stirred at 0° C. for 40 min The reaction was quenched by slow addition of 10% aq citric acid (15 mL) the whole solution was concentrated in vacuo This residue was diluted with EtOAc (200 mL) washed with brine (50 mL) dried over Na2SO4 concentrated in vacuo to give crude product which was purified by column chromatography

Conditions: temp:0.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: To a stirred solution of 3-(tetrahydro-pyran-4-yl)-propionaldehyde (8.59 g, 0.06 mol) and dibenzyl azodicarboxylate (12.8 g, 0.042 mol) in MeCN (250 mL) at 0° C. was added (R-proline) (0.48 g, 0.0042 mol). After stirring the mixture at 0° C. for 15 h, ethanol (100 mL) and NaBH4 (1.56 g, 0.042 mol) were added, and the mixture was stirred at 0° C. for 40 min. The reaction was quenched by slow addition of 10% aq citric acid (15 mL), and the whole solution was concentrated in vacuo. This residue was diluted with EtOAc (200 mL), washed with brine (50 mL), dried over Na2SO4, and concentrated in vacuo to give crude product which was purified by column chromatography to give (S)-dibenzyl 1-(1-hydroxy-3-(tetrahydro-2H-pyran-4-yl)propan-2-yl)hydrazine-1,2-dicarboxylate (16.52 g, 89%). 1H NMR (CD3OD) δ 1.0-1.5 (m, 8H), 2.9-3.3 (m, 2H), 3.4-3.6 (m, 2H), 3.7-3.9 (m, 2H), 4.4-4.7 (m, 2H), 5.1-5.4 (m, 4H), 7.2-7.4 (m, 10H). the mixture was stirred at 0° C. for 40 min The reaction was quenched by slow addition of 10% aq citric acid (15 mL) the whole solution was concentrated in vacuo This residue was diluted with EtOAc (200 mL) washed with brine (50 mL) dried over Na2SO4 concentrated in vacuo to give crude product which was purified by column chromatography

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

Procedure: To a solution of 3-(tetrahydro-pyran-4-yl)-propan-1-ol (11.8 g, 0.0825 mol) in CH2Cl2 (200 mL) was added Dess-Martin periodinane (70.27 g, 0.165 mol). The mixture was stirred at rt. When the reaction was complete, the solution was poured into Et2O (300 mL) and anhydrous K2CO3 (19.84 g, 0.165 mol) was added. The mixture was filtered. The filtrate was dried over Na2SO4, and concentrated under vacuum to give the crude product, which was purified by column chromatography to give 3-(tetrahydro-pyran-4-yl)-propionaldehyde (8.59 g, 83%). 1H NMR (CD3OD) δ 1.1-1.3 (m, 4H), 1.4-1.6 (m, 5H), 2.4-2.5 (t, 2H), 3.2-3.3 (m, 2H), 3.8-3.97 (m, 2H), 9.7-9.8 (s, 1H). was added The mixture was filtered The filtrate was dried over Na2SO4 concentrated under vacuum to give the crude product, which was purified by column chromatography

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

Procedure: To a solution of 3-(tetrahydro-pyran-4-yl)-propan-1-ol (11.8 g, 0.0825 mol) in CH2Cl2 (200 mL) was added Dess-Martin periodinane (70.27 g, 0.165 mol). The mixture was stirred at rt. When the reaction was complete, the solution was poured into Et2O (300 mL) and anhydrous K2CO3 (19.84 g, 0.165 mol) was added. The mixture was filtered. The filtrate was dried over Na2SO4, and concentrated under vacuum to give the crude product, which was purified by column chromatography to give 3-(tetrahydro-pyran-4-yl)-propionaldehyde (8.59 g, 83%). 1H NMR (CD3OD) δ 1.1-1.3 (m, 4H), 1.4-1.6 (m, 5H), 2.4-2.5 (t, 2H), 3.2-3.3 (m, 2H), 3.8-3.97 (m, 2H), 9.7-9.8 (s, 1H). was added The mixture was filtered The filtrate was dried over Na2SO4 concentrated under vacuum to give the crude product, which was purified by column chromatography

Conditions: temp:0.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: To a stirred solution of 3-(tetrahydro-pyran-4-yl)-propionaldehyde (8.59 g, 0.06 mol) and dibenzyl azodicarboxylate (12.8 g, 0.042 mol) in MeCN (250 mL) at 0° C. was added (R-proline) (0.48 g, 0.0042 mol). After stirring the mixture at 0° C. for 15 h, ethanol (100 mL) and NaBH4 (1.56 g, 0.042 mol) were added, and the mixture was stirred at 0° C. for 40 min. The reaction was quenched by slow addition of 10% aq citric acid (15 mL), and the whole solution was concentrated in vacuo. This residue was diluted with EtOAc (200 mL), washed with brine (50 mL), dried over Na2SO4, and concentrated in vacuo to give crude product which was purified by column chromatography to give (S)-dibenzyl 1-(1-hydroxy-3-(tetrahydro-2H-pyran-4-yl)propan-2-yl)hydrazine-1,2-dicarboxylate (16.52 g, 89%). 1H NMR (CD3OD) δ 1.0-1.5 (m, 8H), 2.9-3.3 (m, 2H), 3.4-3.6 (m, 2H), 3.7-3.9 (m, 2H), 4.4-4.7 (m, 2H), 5.1-5.4 (m, 4H), 7.2-7.4 (m, 10H). the mixture was stirred at 0° C. for 40 min The reaction was quenched by slow addition of 10% aq citric acid (15 mL) the whole solution was concentrated in vacuo This residue was diluted with EtOAc (200 mL) washed with brine (50 mL) dried over Na2SO4 concentrated in vacuo to give crude product which was purified by column chromatography

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

Procedure: To a solution of 3-(tetrahydro-pyran-4-yl)-propan-1-ol (11.8 g, 0.0825 mol) in CH2Cl2 (200 mL) was added Dess-Martin periodinane (70.27 g, 0.165 mol). The mixture was stirred at rt. When the reaction was complete, the solution was poured into Et2O (300 mL) and anhydrous K2CO3 (19.84 g, 0.165 mol) was added. The mixture was filtered. The filtrate was dried over Na2SO4, and concentrated under vacuum to give the crude product, which was purified by column chromatography to give 3-(tetrahydro-pyran-4-yl)-propionaldehyde (8.59 g, 83%). 1H NMR (CD3OD) δ 1.1-1.3 (m, 4H), 1.4-1.6 (m, 5H), 2.4-2.5 (t, 2H), 3.2-3.3 (m, 2H), 3.8-3.97 (m, 2H), 9.7-9.8 (s, 1H). was added The mixture was filtered The filtrate was dried over Na2SO4 concentrated under vacuum to give the crude product, which was purified by column chromatography

Conditions: temp:0.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: To a stirred solution of 3-(tetrahydro-pyran-4-yl)-propionaldehyde (8.59 g, 0.06 mol) and dibenzyl azodicarboxylate (12.8 g, 0.042 mol) in MeCN (250 mL) at 0° C. was added (R-proline) (0.48 g, 0.0042 mol). After stirring the mixture at 0° C. for 15 h, ethanol (100 mL) and NaBH4 (1.56 g, 0.042 mol) were added, and the mixture was stirred at 0° C. for 40 min. The reaction was quenched by slow addition of 10% aq citric acid (15 mL), and the whole solution was concentrated in vacuo. This residue was diluted with EtOAc (200 mL), washed with brine (50 mL), dried over Na2SO4, and concentrated in vacuo to give crude product which was purified by column chromatography to give (S)-dibenzyl 1-(1-hydroxy-3-(tetrahydro-2H-pyran-4-yl)propan-2-yl)hydrazine-1,2-dicarboxylate (16.52 g, 89%). 1H NMR (CD3OD) δ 1.0-1.5 (m, 8H), 2.9-3.3 (m, 2H), 3.4-3.6 (m, 2H), 3.7-3.9 (m, 2H), 4.4-4.7 (m, 2H), 5.1-5.4 (m, 4H), 7.2-7.4 (m, 10H). the mixture was stirred at 0° C. for 40 min The reaction was quenched by slow addition of 10% aq citric acid (15 mL) the whole solution was concentrated in vacuo This residue was diluted with EtOAc (200 mL) washed with brine (50 mL) dried over Na2SO4 concentrated in vacuo to give crude product which was purified by column chromatography

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

Procedure: To a solution of 3-(tetrahydro-pyran-4-yl)-propan-1-ol (11.8 g, 0.0825 mol) in CH2Cl2 (200 mL) was added Dess-Martin periodinane (70.27 g, 0.165 mol). The mixture was stirred at rt. When the reaction was complete, the solution was poured into Et2O (300 mL) and anhydrous K2CO3 (19.84 g, 0.165 mol) was added. The mixture was filtered. The filtrate was dried over Na2SO4, and concentrated under vacuum to give the crude product, which was purified by column chromatography to give 3-(tetrahydro-pyran-4-yl)-propionaldehyde (8.59 g, 83%). 1H NMR (CD3OD) δ 1.1-1.3 (m, 4H), 1.4-1.6 (m, 5H), 2.4-2.5 (t, 2H), 3.2-3.3 (m, 2H), 3.8-3.97 (m, 2H), 9.7-9.8 (s, 1H). was added The mixture was filtered The filtrate was dried over Na2SO4 concentrated under vacuum to give the crude product, which was purified by column chromatography