tert-butyl N-(furan-3-yl)carbamate

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

Procedure: To a solution of tert-butyl furan-3-ylcarbamate 32 (1.7 g, 1.0 eq) in THF (50 ml) at −30° C. was added TMEDA (1.75 ml, 1.3 eq) followed by 1.6M solution of n-butyllithium (8.4 ml, 2.25 eq, 1.6M in hexanes). Reaction mixture was allowed to warm up to 0° C. and stirred for 1 h, before being cooled back to −30° C. Dimethyl carbonate (2.4 ml, 3.0 eq) was quickly added, before the reaction mixture was allowed to warm up to room temperature for 1 hr. Reaction mixture was quenched with 2M HCl, followed by addition of saturated aq. NaCl. Mixture was extracted with ethyl acetate. The combined organic extracts were dried with Na2SO4 and concentrated. The crude reaction mixture was purified by flash chromatography to yield tert-butyl 2-(methoxycarbonyl)furan-3-ylcarbamate 33 (1.14 g, 51%): MS (Q1) 242 (M)+. Reaction mixture before being cooled back to −30° C to warm up to room temperature for 1 hr Reaction mixture was quenched with 2M HCl followed by addition of saturated aq. NaCl Mixture was extracted with ethyl acetate The combined organic extracts were dried with Na2SO4 concentrated The crude reaction mixture was purified by flash chromatography

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

Procedure: 3-Furoic acid (5.60 g, 1.0 eq) was dissolved in tert-butanol (200 ml) and treated with triethylamine (10 ml, 1.4 eq) and diphenyl phosphoryl azide (12 ml, 1.1 eq). Mixture was heated at reflux for 18 h. Reaction mixture was cooled to room temperature, then concentrated to 50 ml and poured into saturated aq. NaHCO3. Mixture was stirred at 0° C. for 2 h. Solid was collected by filtration and dried under high vacuum. The crude reaction mixture was purified by flash chromatography to yield tert-butyl furan-3-ylcarbamate 32 (6.95 g, 76%): 1H NMR (CDCl3, 400 MHz) δ 7.71 (bs, 1H), 7.27 (m, 1H), 6.27 (bs, 1H), 6.20 (bs, 1H), 1.50 (s, 9H); MS (Q1) 184 (M)+. Mixture was heated at reflux for 18 h Reaction mixture concentrated to 50 ml poured into saturated aq. NaHCO3 Solid was collected by filtration dried under high vacuum The crude reaction mixture was purified by flash chromatography

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

Procedure: To a solution of tert-butyl furan-3-ylcarbamate 32 (1.7 g, 1.0 eq) in THF (50 ml) at −30° C. was added TMEDA (1.75 ml, 1.3 eq) followed by 1.6M solution of n-butyllithium (8.4 ml, 2.25 eq, 1.6M in hexanes). Reaction mixture was allowed to warm up to 0° C. and stirred for 1 h, before being cooled back to −30° C. Dimethyl carbonate (2.4 ml, 3.0 eq) was quickly added, before the reaction mixture was allowed to warm up to room temperature for 1 hr. Reaction mixture was quenched with 2M HCl, followed by addition of saturated aq. NaCl. Mixture was extracted with ethyl acetate. The combined organic extracts were dried with Na2SO4 and concentrated. The crude reaction mixture was purified by flash chromatography to yield tert-butyl 2-(methoxycarbonyl)furan-3-ylcarbamate 33 (1.14 g, 51%): MS (Q1) 242 (M)+. Reaction mixture before being cooled back to −30° C to warm up to room temperature for 1 hr Reaction mixture was quenched with 2M HCl followed by addition of saturated aq. NaCl Mixture was extracted with ethyl acetate The combined organic extracts were dried with Na2SO4 concentrated The crude reaction mixture was purified by flash chromatography

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

Procedure: 3-Furoic acid (5.60 g, 1.0 eq) was dissolved in tert-butanol (200 ml) and treated with triethylamine (10 ml, 1.4 eq) and diphenyl phosphoryl azide (12 ml, 1.1 eq). Mixture was heated at reflux for 18 h. Reaction mixture was cooled to room temperature, then concentrated to 50 ml and poured into saturated aq. NaHCO3. Mixture was stirred at 0° C. for 2 h. Solid was collected by filtration and dried under high vacuum. The crude reaction mixture was purified by flash chromatography to yield tert-butyl furan-3-ylcarbamate 32 (6.95 g, 76%): 1H NMR (CDCl3, 400 MHz) δ 7.71 (bs, 1H), 7.27 (m, 1H), 6.27 (bs, 1H), 6.20 (bs, 1H), 1.50 (s, 9H); MS (Q1) 184 (M)+. Mixture was heated at reflux for 18 h Reaction mixture concentrated to 50 ml poured into saturated aq. NaHCO3 Solid was collected by filtration dried under high vacuum The crude reaction mixture was purified by flash chromatography

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

Procedure: 3-Furoic acid (5.60 g, 1.0 eq) was dissolved in tert-butanol (200 ml) and treated with triethylamine (10 ml, 1.4 eq) and diphenyl phosphoryl azide (12 ml, 1.1 eq). Mixture was heated at reflux for 18 h. Reaction mixture was cooled to room temperature, then concentrated to 50 ml and poured into saturated aq. NaHCO3. Mixture was stirred at 0° C. for 2 h. Solid was collected by filtration and dried under high vacuum. The crude reaction mixture was purified by flash chromatography to yield tert-butyl furan-3-ylcarbamate 32 (6.95 g, 76%): 1H NMR (CDCl3, 400 MHz) δ 7.71 (bs, 1H), 7.27 (m, 1H), 6.27 (bs, 1H), 6.20 (bs, 1H), 1.50 (s, 9H); MS (Q1) 184 (M)+. Mixture was heated at reflux for 18 h Reaction mixture concentrated to 50 ml poured into saturated aq. NaHCO3 Solid was collected by filtration dried under high vacuum The crude reaction mixture was purified by flash chromatography

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

Procedure: To a solution of tert-butyl furan-3-ylcarbamate 32 (1.7 g, 1.0 eq) in THF (50 ml) at −30° C. was added TMEDA (1.75 ml, 1.3 eq) followed by 1.6M solution of n-butyllithium (8.4 ml, 2.25 eq, 1.6M in hexanes). Reaction mixture was allowed to warm up to 0° C. and stirred for 1 h, before being cooled back to −30° C. Dimethyl carbonate (2.4 ml, 3.0 eq) was quickly added, before the reaction mixture was allowed to warm up to room temperature for 1 hr. Reaction mixture was quenched with 2M HCl, followed by addition of saturated aq. NaCl. Mixture was extracted with ethyl acetate. The combined organic extracts were dried with Na2SO4 and concentrated. The crude reaction mixture was purified by flash chromatography to yield tert-butyl 2-(methoxycarbonyl)furan-3-ylcarbamate 33 (1.14 g, 51%): MS (Q1) 242 (M)+. Reaction mixture before being cooled back to −30° C to warm up to room temperature for 1 hr Reaction mixture was quenched with 2M HCl followed by addition of saturated aq. NaCl Mixture was extracted with ethyl acetate The combined organic extracts were dried with Na2SO4 concentrated The crude reaction mixture was purified by flash chromatography

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

Procedure: To a solution of tert-butyl furan-3-ylcarbamate 32 (1.7 g, 1.0 eq) in THF (50 ml) at −30° C. was added TMEDA (1.75 ml, 1.3 eq) followed by 1.6M solution of n-butyllithium (8.4 ml, 2.25 eq, 1.6M in hexanes). Reaction mixture was allowed to warm up to 0° C. and stirred for 1 h, before being cooled back to −30° C. Dimethyl carbonate (2.4 ml, 3.0 eq) was quickly added, before the reaction mixture was allowed to warm up to room temperature for 1 hr. Reaction mixture was quenched with 2M HCl, followed by addition of saturated aq. NaCl. Mixture was extracted with ethyl acetate. The combined organic extracts were dried with Na2SO4 and concentrated. The crude reaction mixture was purified by flash chromatography to yield tert-butyl 2-(methoxycarbonyl)furan-3-ylcarbamate 33 (1.14 g, 51%): MS (Q1) 242 (M)+. Reaction mixture before being cooled back to −30° C to warm up to room temperature for 1 hr Reaction mixture was quenched with 2M HCl followed by addition of saturated aq. NaCl Mixture was extracted with ethyl acetate The combined organic extracts were dried with Na2SO4 concentrated The crude reaction mixture was purified by flash chromatography

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

Procedure: 3-Furoic acid (5.60 g, 1.0 eq) was dissolved in tert-butanol (200 ml) and treated with triethylamine (10 ml, 1.4 eq) and diphenyl phosphoryl azide (12 ml, 1.1 eq). Mixture was heated at reflux for 18 h. Reaction mixture was cooled to room temperature, then concentrated to 50 ml and poured into saturated aq. NaHCO3. Mixture was stirred at 0° C. for 2 h. Solid was collected by filtration and dried under high vacuum. The crude reaction mixture was purified by flash chromatography to yield tert-butyl furan-3-ylcarbamate 32 (6.95 g, 76%): 1H NMR (CDCl3, 400 MHz) δ 7.71 (bs, 1H), 7.27 (m, 1H), 6.27 (bs, 1H), 6.20 (bs, 1H), 1.50 (s, 9H); MS (Q1) 184 (M)+. Mixture was heated at reflux for 18 h Reaction mixture concentrated to 50 ml poured into saturated aq. NaHCO3 Solid was collected by filtration dried under high vacuum The crude reaction mixture was purified by flash chromatography

Conditions: temp:-40.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: Butyl lithium (as 1.6 M in hexanes, 45 mL) was added slowly to a solution of tert-butyl 3-furylcarbamate (Intermediate 80) (5.49 g) in THF (60 mL) at −40° C., keeping the internal reaction temperature less than −35° C. The reaction was stirred at −40° C. for 4 hours, then poured onto solid CO2 (100 mL) under a blanket of diethyl ether (300 mL). After warming to ambient temperature, the mixture was poured into water (300 mL) with stirring and an additional 100 mL diethyl ether added. The phases were separated and the organic phase was further extracted into water (2×100 mL). The combined organic phases were washed with ether, acidified by addition of aqueous HCl, and extracted into EtOAc (4×250 mL). The combined extracts were dried and evaporated to give a pale yellow solid (7.5 g). This was triturated with cyclohexane to afford the title compound as a white solid (4.80 g, 70%); the internal reaction temperature less than −35° C After warming to ambient temperature with stirring The phases were separated the organic phase was further extracted into water (2×100 mL) The combined organic phases were washed with ether acidified by addition of aqueous HCl extracted into EtOAc (4×250 mL) The combined extracts were dried evaporated

Conditions: temp:-40.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: Butyl lithium (as 1.6 M in hexanes, 45 mL) was added slowly to a solution of tert-butyl 3-furylcarbamate (Intermediate 80) (5.49 g) in THF (60 mL) at −40° C., keeping the internal reaction temperature less than −35° C. The reaction was stirred at −40° C. for 4 hours, then poured onto solid CO2 (100 mL) under a blanket of diethyl ether (300 mL). After warming to ambient temperature, the mixture was poured into water (300 mL) with stirring and an additional 100 mL diethyl ether added. The phases were separated and the organic phase was further extracted into water (2×100 mL). The combined organic phases were washed with ether, acidified by addition of aqueous HCl, and extracted into EtOAc (4×250 mL). The combined extracts were dried and evaporated to give a pale yellow solid (7.5 g). This was triturated with cyclohexane to afford the title compound as a white solid (4.80 g, 70%); the internal reaction temperature less than −35° C After warming to ambient temperature with stirring The phases were separated the organic phase was further extracted into water (2×100 mL) The combined organic phases were washed with ether acidified by addition of aqueous HCl extracted into EtOAc (4×250 mL) The combined extracts were dried evaporated

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

Procedure: To a solution of tert-butyl furan-3-ylcarbamate (1.7 g, 1.0 eq) in THF (50 ml) at −30° C. was added TMEDA (1.75 ml, 1.3 eq) followed by 1.6M solution of n-butyllithium (8.4 ml, 2.25 eq, 1.6M in hexanes). Reaction mixture was allowed to warm up to 0° C. and stirred for 1 h, before being cooled back to −30° C. Dimethyl carbonate (2.4 ml, 3.0 eq) was quickly added, before the reaction mixture was allowed to warm up to room temperature for 1 hr. Reaction mixture was quenched with 2M HCl, followed by addition of saturated aq. NaCl. Mixture was extracted with ethyl acetate. The combined organic extracts were dried with Na2SO4 and concentrated. The crude reaction mixture was purified by flash chromatography to yield tert-butyl 2-(methoxycarbonyl)furan-3-ylcarbamate (1.14 g, 51%): MS (Q1) 242 (M)+. Reaction mixture before being cooled back to −30° C to warm up to room temperature for 1 hr Reaction mixture was quenched with 2M HCl followed by addition of saturated aq. NaCl Mixture was extracted with ethyl acetate The combined organic extracts were dried with Na2SO4 concentrated The crude reaction mixture was purified by flash chromatography

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

Procedure: 3-Furoic acid (5.60 g, 1.0 eq) was dissolved in tert-butanol (200 ml) and treated with triethylamine (10 ml, 1.4 eq) and diphenyl phosphoryl azide (12 ml, 1.1 eq). Mixture was heated at reflux for 18 h. Reaction mixture was cooled to room temperature, then concentrated to 50 ml and poured into saturated aq. NaHCO3. Mixture was stirred at 0° C. for 2 h. Solid was collected by filtration and dried under high vacuum. The crude reaction mixture was purified by flash chromatography to yield tert-butyl furan-3-ylcarbamate (6.95 g, 76%): 1H NMR (CDCl3, 400 MHz) δ 7.71 (bs, 1H), 7.27 (m, 1H), 6.27 (bs, 1H), 6.20 (bs, 1H), 1.50 (s, 9H); MS (Q1) 184 (M)+. Mixture was heated at reflux for 18 h Reaction mixture concentrated to 50 ml poured into saturated aq. NaHCO3 Solid was collected by filtration dried under high vacuum The crude reaction mixture was purified by flash chromatography