methyl benzenesulfinate

Conditions: temp:0.00; pressure:0.00; stir:

Conditions: temp:0.00; pressure:0.00; stir:

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

Procedure: To potassium hydride (35 weight % in oil, washed with heptane (×3), 3.01 g, 26.3 mmol), in THF (20 mL) was added a solution of (3S,7aS)-7a-cyclopropyl-3-phenyltetrahydropyrrolo[2,1-b]oxazol-5(6H)-one (preparation #23) (2.56 g, 10.5 mmol) in THF (20 mL) dropwise via an addition funnel. A solution of methyl benzenesulfinate (1.97 g, 12.6 mmol) in THF (20 mL) was then added dropwise via an addition funnel. The reaction mixture was stirred at ambient temperature for about 16 hours. The reaction was quenched by the addition of water (4.2 mL). The mixture was concentrated and the residue was partitioned between 0.5 M H3PO4 (100 mL) and DCM (200 mL). The layers were separated and the aqueous layer was extracted with DCM (3×100 mL). The combined organic extracts were washed with brine, dried over MgSO4, filtered and concentrated to yield a light brown solid. Toluene (83 mL) was added followed by solid Na2CO3 (10.35 g). The reaction mixture was refluxed for about 16 hours and then filtered and concentrated in vacuo. The residue was purified on a Biotage silica gel column eluting with heptane/EtOAc (4:1). A second purification on silica gel eluting DCM/EtOAc (1:0 to 4:1) afforded (3S,7aR)-7a-cyclopropyl-3-phenyl-2,3-dihydropyrrolo[2,1-b]oxazol-5(7aH)-one (1.82 g, 7.57 mmol). 1H NMR (CDCl3-d) δ 7.34 (m, 4H), 7.28 (m, 1H), 7.11 (d, 1H), 6.08 (d, 1H), 5.06 (t, 1H), 4.69 (t, 1H), 4.43 (dd, 1H), 1.14 (m, 1H), 0.45 (m, 2H), 0.32 (m, 1H), 0.21 (m, 1H). The reaction was quenched by the addition of water (4.2 mL) The mixture was concentrated the residue was partitioned between 0.5 M H3PO4 (100 mL) and DCM (200 mL) The layers were separated the aqueous layer was extracted with DCM (3×100 mL) The combined organic extracts were washed with brine dried over MgSO4 filtered concentrated to yield a light brown solid The reaction mixture was refluxed for about 16 hours filtered concentrated in vacuo The residue was purified on a Biotage silica gel column eluting with heptane/EtOAc (4:1) A second purification on silica gel eluting DCM/EtOAc (1:0 to 4:1)

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

Procedure: To a solution of the 9-[(phenyl)methyl]-5-carbomethoxy-1,2-dihydrocarbazol-4(3H)-one (2.87 g, 8.61 mM) in 29 ml dioxane was added 60% sodium hydride in mineral oil (0.79 g, 19.8 mM). The reaction was stirred 8 minutes, then methyl benzenesulfinate (1.80 ml, 13.8 mM) was added. The reaction was stirred an additional 1.5 hours, then diluted with 43 ml dioxane and 1.13 ml acetic acid. The mixture was refluxed 1 hour, diluted with ethyl acetate, and extracted with saturated NaHCO3 two times, then with brine. After drying (NaSO4), evaporation in vacuo afforded 4.90 g. The mixture was purified by column chromatography on silica gel (elution with toluene/methylene chloride) to afford 2.31 g (81%) of the 9-[(phenyl)methyl]-4-hydroxy-5-carbomethoxy carbazole. 1H NMR (DMSO-d6) δ 10.25 (s, 1H), 7.7 (d, 1H, J=8 Hz), 7.4 (t, 1H, J=8 Hz), 7.4-7.0 (m, 8H), 6.6 (d, 1H, J=8 Hz), 5.6 (s, 2H), and 3.8 (s, 3H). IR (CHCl3, cm−1) 1723, 1685, 1621, 1597, 1568, 1496, 1453, 1442, 1392, 1286, 1267, 1156, and 1138. MS (ES) m/e 330, 332. The reaction was stirred an additional 1.5 hours The mixture was refluxed 1 hour extracted with saturated NaHCO3 two times After drying (NaSO4), evaporation in vacuo afforded 4.90 g The mixture was purified by column chromatography on silica gel (elution with toluene/methylene chloride)

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

Procedure: To a solution of the 9-[(phenyl)methyl]-5-carbomethoxy-1,2-dihydrocarbazol-4(3H)-one (2.87 g, 8.61 mM) in 29 ml dioxane was added 60% sodium hydride in mineral oil (0.79 g, 19.8 mM). The reaction was stirred 8 minutes, then methyl benzenesulfinate (1.80 ml, 13.8 mM) was added. The reaction was stirred an additional 1.5 h, then diluted with 43 ml dioxane and 1.13 ml acetic acid. The mixture was refluxed 1 h, diluted with ethyl acetate, and extracted with sat'd NaHCO3 two times, then with brine. After drying (NaSO4), evaporation in vacuo afforded 4.90 g. The mixture was purified by column chromatography on silica gel (elution with toluene/methylene chloride) to afford 2.31 g (81%) of the 9-[(phenyl)methyl]-4-hydroxy-5-carbomethoxy carbazole. 1H NMR (DMSO-d6) δ 10.25 (s, 1H), 7.7 (d, 1H, J=8 Hz), 7.4 (t, 1H, J=8 Hz), 7.4-7.0 (m, 8H), 6.6 (d, 1H, J=8 Hz), 5.6 (s, 2H), and 3.8 (s, 3H). IR (CHCl3, cm−1) 1723, 1685, 1621, 1597, 1568, 1496, 1453, 1442, 1392, 1286, 1267, 1156, and 1138. MS (ES) m/e 330, 332. The reaction was stirred an additional 1.5 h The mixture was refluxed 1 h extracted with sat'd NaHCO3 two times After drying (NaSO4), evaporation in vacuo afforded 4.90 g The mixture was purified by column chromatography on silica gel (elution with toluene/methylene chloride)

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

Procedure: To a solution of 9-[(3-methylphenyl)methyl]-5-carbomethoxy-2-methyl-1,2-dihydrocarbazol-4(3H)-one (1.41 g, 3.89 mM) in 13 ml dioxane was added 60% sodium hydride in mineral oil (0.36 g, 8.95 mM). The reaction was stirred 6 minutes, then methyl benzenesulfinate (0.81 ml, 6.22 mM) was added. The reaction was stirred an additional 6 hours, then diluted with 20 ml dioxane and 0.51 ml acetic acid. The mixture was refluxed 30 minutes, diluted with ethyl acetate, and extracted with saturated NaHCO3, brine, then water. After drying (NaSO4), evaporation in vacuo afforded 2.30 g. The mixture was purified by column chromatography on silica gel (elution with toluene/methylene chloride) to afford 0.92 g (66%) of 9-[(3-methylphenyl)methyl]-2-methyl-4-hydroxy-5-carbomethoxy carbazole. 1H NMR (CDCl3) δ 10.45 (s, 1H), 8.0 (d, J=8 Hz, 1H), 7.55 (d, J=8 Hz, 1H), 7.4 (dd, J=8 and 8 Hz, 1H), 7.4 (dd, J=8 and 8 Hz, 1H), 7.05 (d, J=8 HZ, 1H), 6.9 (s, 1H), 6.85 (d, J=8 Hz, 1H), 6.75 (s, 1H), 6.7 (s, 1H), 5.45 (s, 2H), 4.1 (s, 3H), 2.4 (s, 3H), 2.25 (s, 3H). MS (ES) m/e 328, 360. The reaction was stirred an additional 6 hours The mixture was refluxed 30 minutes extracted with saturated NaHCO3, brine After drying (NaSO4), evaporation in vacuo afforded 2.30 g The mixture was purified by column chromatography on silica gel (elution with toluene/methylene chloride)

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

Procedure: To a solution of 9-[(3-methylphenyl)methyl]-5-carbomethoxy-2-methyl-1,2-dihydrocarbazol-4(3H)-one (1.41 g, 3.89 mM) in 13 ml dioxane was added 60% sodium hydride in mineral oil (0.36 g, 8.95 mM). The reaction was stirred 6 minutes, then methyl benzenesulfinate (0.81 ml, 6.22 mM) was added. The reaction was stirred an additional 6 hours, then diluted with 20 ml dioxane and 0.51 ml acetic acid. The mixture was refluxed 30 minutes, diluted with ethyl acetate, and extracted with saturated NaHCO3, brine, then water. After drying (NaSO4), evaporation in vacuo afforded 2.30 g. The mixture was purified by column chromatography on silica gel (elution with toluene/methylene chloride) to afford 0.92 g (66%) of 9-[(3-methylphenyl)methyl]-2-methyl-4-hydroxy-5-carbomethoxy carbazole. 1H NMR (CDCl3) δ 10.45 (s, 1H), 8.0 (d, J=8 Hz, 1H), 7.55 (d, J=8 Hz, 1H), 7.4 (dd, J=8 and 8 Hz, 1H), 7.4 (dd, J=8 and 8 Hz, 1H), 7.05 (d, J=8 HZ, 1H), 6.9 (s, 1H), 6.85 (d, J=8 Hz, 1H), 6.75 (s, 1H), 6.7 (s, 1H), 5.45 (s, 2H), 4.1 (s, 3H), 2.4 (s, 3H), 2.25 (s, 3H). MS (ES) m/e 328, 360. The reaction was stirred an additional 6 hours The mixture was refluxed 30 minutes extracted with saturated NaHCO3, brine After drying (NaSO4), evaporation in vacuo afforded 2.30 g The mixture was purified by column chromatography on silica gel (elution with toluene/methylene chloride)

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

Procedure: To potassium hydride (35 weight % in oil, washed with heptane (×3), 3.01 g, 26.3 mmol), in THF (20 mL) was added a solution of (3S,7aS)-7a-cyclopropyl-3-phenyltetrahydropyrrolo[2,1-b]oxazol-5(6H)-one (preparation #23) (2.56 g, 10.5 mmol) in THF (20 mL) dropwise via an addition funnel. A solution of methyl benzenesulfinate (1.97 g, 12.6 mmol) in THF (20 mL) was then added dropwise via an addition funnel. The reaction mixture was stirred at ambient temperature for about 16 hours. The reaction was quenched by the addition of water (4.2 mL). The mixture was concentrated and the residue was partitioned between 0.5 M H3PO4 (100 mL) and DCM (200 mL). The layers were separated and the aqueous layer was extracted with DCM (3×100 mL). The combined organic extracts were washed with brine, dried over MgSO4, filtered and concentrated to yield a light brown solid. Toluene (83 mL) was added followed by solid Na2CO3 (10.35 g). The reaction mixture was refluxed for about 16 hours and then filtered and concentrated in vacuo. The residue was purified on a Biotage silica gel column eluting with heptane/EtOAc (4:1). A second purification on silica gel eluting DCM/EtOAc (1:0 to 4:1) afforded (3S,7aR)-7a-cyclopropyl-3-phenyl-2,3-dihydropyrrolo[2,1-b]oxazol-5(7aH)-one (1.82 g, 7.57 mmol). 1H NMR (CDCl3-d) δ 7.34 (m, 4H), 7.28 (m, 1H), 7.11 (d, 1H), 6.08 (d, 1H), 5.06 (t, 1H), 4.69 (t, 1H), 4.43 (dd, 1H), 1.14 (m, 1H), 0.45 (m, 2H), 0.32 (m, 1H), 0.21 (m, 1H). The reaction was quenched by the addition of water (4.2 mL) The mixture was concentrated the residue was partitioned between 0.5 M H3PO4 (100 mL) and DCM (200 mL) The layers were separated the aqueous layer was extracted with DCM (3×100 mL) The combined organic extracts were washed with brine dried over MgSO4 filtered concentrated to yield a light brown solid The reaction mixture was refluxed for about 16 hours filtered concentrated in vacuo The residue was purified on a Biotage silica gel column eluting with heptane/EtOAc (4:1) A second purification on silica gel eluting DCM/EtOAc (1:0 to 4:1)

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

Procedure: To potassium hydride (35 weight % in oil, washed with heptane (×3), 3.01 g, 26.3 mmol), in THF (20 mL) was added a solution of (3S,7aS)-7a-cyclopropyl-3-phenyltetrahydropyrrolo[2,1-b]oxazol-5(6H)-one (preparation #23) (2.56 g, 10.5 mmol) in THF (20 mL) dropwise via an addition funnel. A solution of methyl benzenesulfinate (1.97 g, 12.6 mmol) in THF (20 mL) was then added dropwise via an addition funnel. The reaction mixture was stirred at ambient temperature for about 16 hours. The reaction was quenched by the addition of water (4.2 mL). The mixture was concentrated and the residue was partitioned between 0.5 M H3PO4 (100 mL) and DCM (200 mL). The layers were separated and the aqueous layer was extracted with DCM (3×100 mL). The combined organic extracts were washed with brine, dried over MgSO4, filtered and concentrated to yield a light brown solid. Toluene (83 mL) was added followed by solid Na2CO3 (10.35 g). The reaction mixture was refluxed for about 16 hours and then filtered and concentrated in vacuo. The residue was purified on a Biotage silica gel column eluting with heptane/EtOAc (4:1). A second purification on silica gel eluting DCM/EtOAc (1:0 to 4:1) afforded (3S,7aR)-7a-cyclopropyl-3-phenyl-2,3-dihydropyrrolo[2,1-b]oxazol-5(7aH)-one (1.82 g, 7.57 mmol). 1H NMR (CDCl3-d) δ 7.34 (m, 4H), 7.28 (m, 1H), 7.11 (d, 1H), 6.08 (d, 1H), 5.06 (t, 1H), 4.69 (t, 1H), 4.43 (dd, 1H), 1.14 (m, 1H), 0.45 (m, 2H), 0.32 (m, 1H), 0.21 (m, 1H). The reaction was quenched by the addition of water (4.2 mL) The mixture was concentrated the residue was partitioned between 0.5 M H3PO4 (100 mL) and DCM (200 mL) The layers were separated the aqueous layer was extracted with DCM (3×100 mL) The combined organic extracts were washed with brine dried over MgSO4 filtered concentrated to yield a light brown solid The reaction mixture was refluxed for about 16 hours filtered concentrated in vacuo The residue was purified on a Biotage silica gel column eluting with heptane/EtOAc (4:1) A second purification on silica gel eluting DCM/EtOAc (1:0 to 4:1)

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

Procedure: To a solution of the 9-[(phenyl)methyl]-5-carbomethoxy-1,2-dihydrocarbazol-4(3H)-one (2.87 g, 8.61 mM) in 29 ml dioxane was added 60% sodium hydride in mineral oil (0.79 g, 19.8 mM). The reaction was stirred 8 minutes, then methyl benzenesulfinate (1.80 ml, 13.8 mM) was added. The reaction was stirred an additional 1.5 h, then diluted with 43 ml dioxane and 1.13 ml acetic acid. The mixture was refluxed 1 h, diluted with ethyl acetate, and extracted with sat'd NaHCO3 two times, then with brine. After drying (NaSO4), evaporation in vacuo afforded 4.90 g. The mixture was purified by column chromatography on silica gel (elution with toluene/methylene chloride) to afford 2.31 g (81%) of the 9-[(phenyl)methyl]-4-hydroxy-5-carbomethoxy carbazole. 1H NMR (DMSO-d6) δ10.25 (s, 1H), 7.7 (d, 1H, J=8 Hz), 7.4 (t, 1H, J=8 Hz), 7.4-7.0 (m, 8H), 6.6 (d, 1H, J=8 Hz), 5.6 (s, 2H), and 3.8 (s, 3H). IR (CHCl3, cm−1) 1723, 1685, 1621, 1597, 1568, 1496, 1453, 1442, 1392, 1286, 1267, 1156, and 1138. MS (ES) m/e 330, 332. The reaction was stirred an additional 1.5 h The mixture was refluxed 1 h extracted with sat'd NaHCO3 two times After drying (NaSO4), evaporation in vacuo afforded 4.90 g The mixture was purified by column chromatography on silica gel (elution with toluene/methylene chloride)

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

Procedure: To a solution of 9-[(3-methylphenyl)methyl]-5-carbomethoxy-2-methyl-1,2-dihydrocarbazol-4(3H)-one (1.41 g, 3.89 mM) in 13 ml dioxane was added 60% sodium hydride in mineral oil (0.36 g, 8.95 mM). The reaction was stirred 6 minutes, then methyl benzenesulfinate (0.81 ml, 6.22 mM) was added. The reaction was stirred an additional 6 hours, then diluted with 20 ml dioxane and 0.51 ml acetic acid. The mixture was refluxed 30 minutes, diluted with ethyl acetate, and extracted with saturated NaHCO3, brine, then water. After drying (NaSO4), evaporation in vacuo afforded 2.30 g. The mixture was purified by column chromatography on silica gel (elution with toluene/methylene chloride) to afford 0.92 g (66%) of 9-[(3-methylphenyl)methyl]-2-methyl-4-hydroxy-5-carbomethoxy carbazole. 1H NMR (CDCl3) δ10.45 (s, 1H), 8.0 (d, J=8 Hz, 1H), 7.55 (d, J=8 Hz, 1H), 7.4 (dd, J=8 and 8 Hz, 1H), 7.4 (dd, J=8 and 8 Hz, 1H), 7.05 (d, J=8 HZ, 1H), 6.9 (s, 1H), 6.85 (d, J=8 Hz, 1H), 6.75 (s, 1H), 6.7 (s, 1H), 5.45 (s, 2H), 4.1 (s, 3H), 2.4 (s, 3H), 2.25 (s, 3H). MS (ES) m/e 328, 360. The reaction was stirred an additional 6 hours The mixture was refluxed 30 minutes extracted with saturated NaHCO3, brine After drying (NaSO4), evaporation in vacuo afforded 2.30 g The mixture was purified by column chromatography on silica gel (elution with toluene/methylene chloride)

Conditions: temp:0.00; pressure:0.00; stir: