tert-butyl (3aR,4R,6aS)-4-(hydroxymethyl)-2,2-dimethyl-3a,4,6,6a-tetrahydro-[1,3]dioxolo[4,5-c]pyrrole-5-carboxylate

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

Procedure: To a solution of (S)-1-tert-butyl 2-methyl 1H-pyrrole-1,2(2H,5H)-dicarboxylate (1.0 g, 4.5 mmol) in dioxane —H2O (4:1) was added NMO (580 mg, 4.95 mmol) and OsO4 114 mg, 0.45 mmol, 2.5 wt % in H2O) and the reaction mixture was stirred for 24 h at r.t. Quenched with 10% aqueous Na2S2O3 solution and extracted with ethyl acetate. The combined organic layers washed with brine and dried over anhydrous Na2SO4. The resultant residue was dissolved in acetone (5 mL), added catalytic amount of PPTS and dimethoxy propane (1.5 mL). The reaction mixture was stirred over night at r.t. and diluted with ethyl acetate, washed with saturated NaHCO3 and brine. Dried over anhydrous Na2SO4 and concentrated under reduced pressure. The residue was dissolved in ether (5.0 mL) and LiAlH4 (3.0 mL, 3.0 mmol, 1M solution in ether) was added at 0° C. under N2 atmosphere. Stirred for 1 h and quenched with 1N NaOH (0.1 mL) solution. Anhydrous MgSO4 was added and filtered through celite. The filtrate was concentrated under reduced pressure and purified by flash chromatography (5% MeOH—CH2Cl2) to afford (3aR,4R,6aS)-tert-butyl 4-(hydroxymethyl)-2,2-dimethyldihydro-3aH-[1,3]dioxolo[4,5-c]pyrrole-5(4H)-carboxylate (550 mg, 45%, over 3 steps). 1H NMR (400 MHz, CHLOROFORM-d) δ ppm 1.32 (s, 6H) 1.47 (s, 9H) 3.33-3.38 (m, 1H) 3.50 (dd, J=13.14, 6.06 Hz, 2H) 4.54 (d, J=3.79 Hz, 1H) 4.59-4.61 (m, 1H) 4.66-4.73 (m, 2H). Quenched with 10% aqueous Na2S2O3 solution extracted with ethyl acetate The combined organic layers washed with brine dried over anhydrous Na2SO4 The resultant residue was dissolved in acetone (5 mL) added catalytic amount of PPTS and dimethoxy propane (1.5 mL) The reaction mixture was stirred over night at r.t. diluted with ethyl acetate washed with saturated NaHCO3 and brine Dried over anhydrous Na2SO4 concentrated under reduced pressure The residue was dissolved in ether (5.0 mL) Stirred for 1 h quenched with 1N NaOH (0.1 mL) solution Anhydrous MgSO4 was added filtered through celite The filtrate was concentrated under reduced pressure purified by flash chromatography (5% MeOH—CH2Cl2)

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

Procedure: To a solution of (S)-1-tert-butyl 2-methyl 1H-pyrrole-1,2(2H,5H)-dicarboxylate (1.0 g, 4.5 mmol) in dioxane —H2O (4:1) was added NMO (580 mg, 4.95 mmol) and OsO4 114 mg, 0.45 mmol, 2.5 wt % in H2O) and the reaction mixture was stirred for 24 h at r.t. Quenched with 10% aqueous Na2S2O3 solution and extracted with ethyl acetate. The combined organic layers washed with brine and dried over anhydrous Na2SO4. The resultant residue was dissolved in acetone (5 mL), added catalytic amount of PPTS and dimethoxy propane (1.5 mL). The reaction mixture was stirred over night at r.t. and diluted with ethyl acetate, washed with saturated NaHCO3 and brine. Dried over anhydrous Na2SO4 and concentrated under reduced pressure. The residue was dissolved in ether (5.0 mL) and LiAlH4 (3.0 mL, 3.0 mmol, 1M solution in ether) was added at 0° C. under N2 atmosphere. Stirred for 1 h and quenched with 1N NaOH (0.1 mL) solution. Anhydrous MgSO4 was added and filtered through celite. The filtrate was concentrated under reduced pressure and purified by flash chromatography (5% MeOH—CH2Cl2) to afford (3aR,4R,6aS)-tert-butyl 4-(hydroxymethyl)-2,2-dimethyldihydro-3aH-[1,3]dioxolo[4,5-c]pyrrole-5(4H)-carboxylate (550 mg, 45%, over 3 steps). 1H NMR (400 MHz, CHLOROFORM-d) δ ppm 1.32 (s, 6H) 1.47 (s, 9H) 3.33-3.38 (m, 1H) 3.50 (dd, J=13.14, 6.06 Hz, 2H) 4.54 (d, J=3.79 Hz, 1H) 4.59-4.61 (m, 1H) 4.66-4.73 (m, 2H). Quenched with 10% aqueous Na2S2O3 solution extracted with ethyl acetate The combined organic layers washed with brine dried over anhydrous Na2SO4 The resultant residue was dissolved in acetone (5 mL) added catalytic amount of PPTS and dimethoxy propane (1.5 mL) The reaction mixture was stirred over night at r.t. diluted with ethyl acetate washed with saturated NaHCO3 and brine Dried over anhydrous Na2SO4 concentrated under reduced pressure The residue was dissolved in ether (5.0 mL) Stirred for 1 h quenched with 1N NaOH (0.1 mL) solution Anhydrous MgSO4 was added filtered through celite The filtrate was concentrated under reduced pressure purified by flash chromatography (5% MeOH—CH2Cl2)

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

Procedure: To a solution of (S)-1-tert-butyl 2-methyl 1H-pyrrole-1,2(2H, 5H)-dicarboxylate (1.0 g, 4.5 mmol) in dioxane —H2O (4:1) was added NMO (580 mg, 4.95 mmol) and OsO4 114 mg, 0.45 mmol, 2.5 wt % in H2O) and the reaction mixture was stirred for 24 h at r.t. Quenched with 10% aqueous Na2S2O3 solution and extracted with ethyl acetate. The combined organic layers washed with brine and dried over anhydrous Na2SO4. The resultant residue was dissolved in acetone (5 mL), added catalytic amount of PPTS and dimethoxy propane (1.5 mL). The reaction mixture was stirred over night at r.t. and diluted with ethyl acetate, washed with saturated NaHCO3 and brine. Dried over anhydrous Na2SO4 and concentrated under reduced pressure. The residue was dissolved in ether (5.0 mL) and LiAlH4 (3.0 mL, 3.0 mmol, 1M solution in ether) was added at 0° C. under N2 atmosphere. Stirred for 1 h and quenched with 1N NaOH (0.1 mL) solution. Anhydrous MgSO4 was added and filtered through celite. The filtrate was concentrated under reduced pressure and purified by flash chromatography (5% MeOH—CH2Cl2) to afford (3aR,4R,6aS)-tert-butyl 4-(hydroxymethyl)-2,2-dimethyldihydro-3aH-[1,3]dioxolo[4,5-c]pyrrole-5(4H)-carboxylate (550 mg, 45%, over 3 steps). 1H NMR (400 MHz, CHLOROFORM-d) δ ppm 1.32 (s, 6H) 1.47 (s, 9H) 3.33-3.38 (m, 1H) 3.50 (dd, J=13.14, 6.06 Hz, 2H) 4.54 (d, J=3.79 Hz, 1H) 4.59-4.61 (m, 1H) 4.66-4.73 (m, 2H). Quenched with 10% aqueous Na2S2O3 solution extracted with ethyl acetate The combined organic layers washed with brine dried over anhydrous Na2SO4 The resultant residue was dissolved in acetone (5 mL) added catalytic amount of PPTS and dimethoxy propane (1.5 mL) The reaction mixture was stirred over night at r.t. diluted with ethyl acetate washed with saturated NaHCO3 and brine Dried over anhydrous Na2SO4 concentrated under reduced pressure The residue was dissolved in ether (5.0 mL) Stirred for 1 h quenched with 1N NaOH (0.1 mL) solution Anhydrous MgSO4 was added filtered through celite The filtrate was concentrated under reduced pressure purified by flash chromatography (5% MeOH—CH2Cl2)

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

Procedure: To a solution of (S)-1-tert-butyl 2-methyl 1H-pyrrole-1,2(2H,5H)-dicarboxylate (1.0 g, 4.5 mmol) in dioxane —H2O (4:1) was added NMO (580 mg, 4.95 mmol) and OsO4 114 mg, 0.45 mmol, 2.5 wt % in H2O) and the reaction mixture was stirred for 24 h at r.t. Quenched with 10% aqueous Na2S2O3 solution and extracted with ethyl acetate. The combined organic layers washed with brine and dried over anhydrous Na2SO4. The resultant residue was dissolved in acetone (5 mL), added catalytic amount of PPTS and dimethoxy propane (1.5 mL). The reaction mixture was stirred over night at r.t. and diluted with ethyl acetate, washed with saturated NaHCO3 and brine. Dried over anhydrous Na2SO4 and concentrated under reduced pressure. The residue was dissolved in ether (5.0 mL) and LiAlH4 (3.0 mL, 3.0 mmol, 1M solution in ether) was added at 0° C. under N2 atmosphere. Stirred for 1 h and quenched with 1N NaOH (0.1 mL) solution. Anhydrous MgSO4 was added and filtered through celite. The filtrate was concentrated under reduced pressure and purified by flash chromatography (5% MeOH—CH2Cl2) to afford (3aR,4R,6aS)-tert-butyl 4-(hydroxymethyl)-2,2-dimethyldihydro-3aH-[1,3]dioxolo[4,5-c]pyrrole-5(4H)-carboxylate (550 mg, 45%, over 3 steps). 1H NMR (400 MHz, CHLOROFORM-d) δ ppm 1.32 (s, 6H) 1.47 (s, 9H) 3.33-3.38 (m, 1H) 3.50 (dd, J=13.14, 6.06 Hz, 2H) 4.54 (d, J=3.79 Hz, 1H) 4.59-4.61 (m, 1H) 4.66-4.73 (m, 2H). Quenched with 10% aqueous Na2S2O3 solution extracted with ethyl acetate The combined organic layers washed with brine dried over anhydrous Na2SO4 The resultant residue was dissolved in acetone (5 mL) added catalytic amount of PPTS and dimethoxy propane (1.5 mL) The reaction mixture was stirred over night at r.t. diluted with ethyl acetate washed with saturated NaHCO3 and brine Dried over anhydrous Na2SO4 concentrated under reduced pressure The residue was dissolved in ether (5.0 mL) Stirred for 1 h quenched with 1N NaOH (0.1 mL) solution Anhydrous MgSO4 was added filtered through celite The filtrate was concentrated under reduced pressure purified by flash chromatography (5% MeOH—CH2Cl2)