* All experimental methods are cited from the reference, please refer to the original source for details. We do not guarantee the accuracy of the content in the reference.
With diphenyl phosphoryl azide; triethylamine In toluene at 20℃; Reflux
e. To a solution of 3-furoic acid 96 (54.4 g, 485 mmol), triethylamine (105 ml, 753 mmol), tert-butanol (25.2 mL, 786 mmol) in toluene (800 mL) was added dropwise at room temperature over 45 min period diphenyl phosphoryl azide (157.8 mL, 732 mmol). The resulting solution was heated at reflux for 6 h and at room temperature overnight. The reaction was diluted with water (1000 mL) and extracted twice with ethyl acetate (1000 ml). The organic layers were combined washed with water (800 mL), brine (800 mL), decolorized with activated charcoal, dried, filtered and concentrated in vacuo to furnish a brown semisolid. The semisolid was crystallized from dichloromethane (300 mL) and hexanes (600 mL) to furnish tert-butyl furan-3-ylcarbamate 97 (61.5 g, 78percent). 1H NMR (300 MHz, CDC13) δ 7.71 (s, IH), 7.30 - 7.24 (m, IH), 6.43 (s, IH), 6.27 (s, IH), 1.75 - 1.32 (s, 9H).
76%
Stage #1: for 18 h; Heating / reflux Stage #2: With sodium hydrogencarbonate In water at 0℃; for 2 h;
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, 76percent): 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)+.
76%
Stage #1: for 18 h; Heating / reflux Stage #2: With sodium hydrogencarbonate In water at 0℃; for 2 h;
3-Furoic acid (5.6Og, 1.0 eq) was dissolved in fert-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, 76percent) : 1H NMR (CDCl3, 400 MHz) δ 7.71 (bs, IH), 7.27 (m, IH), 6.27 (bs, IH), <n="139"/>6.20 (bs, IH), 1.50 (s, 9H) ; MS (Ql) 184 (M)+.
76%
Stage #1: for 18 h; Heating / reflux Stage #2: at 0℃; for 2 h;
3-Furoic acid (5.6Og, 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 0C 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, 76percent) : 1H NMR (CDCl3, 400 MHz) δ 7.71 (bs, IH), 7.27 (m, IH), 6.27 (bs, IH), 6.20 (bs, IH), 1.50 (s, 9H) ; MS (Ql) 184 (M)+.
71%
With diphenyl phosphoryl azide; triethylamine In toluene for 6 h; Heating / reflux
Diphenylphosphoryl azide (78.9 mL) was added dropwise to a solution of 3-furoic acid (Aldrich) (27.2 g) in a mixture of toluene (400 mL), triethylamine (52.5 [ML)] and tert- butanol (35.1 [ML).] The solution was heated to reflux for 6 hours, cooled overnight and water added (500 mL). The mixture was extracted into EtOAc (3 x 500 mL) and the combined organics washed with water [(400 ML), BRINE] (400 mL), decolourised over activated charcoal, dried [(MGS04),] and the solvent removed to give 73 g of a brownish solid. Trituration with 1: 1 [DCM/ISOHEXANE] gave the title compound as a white solid (31.5 g, 71percent) ; [1H] NMR [(CDC13)] [8 1.] 50 (s, 9H), 6.22 (s, br, 1H), 6.27 (s, 1H), 7.26 (d, 1H), 7.69 (s, br, [1H)] ; MS [M/E] [MU 184.]
70%
at 90℃; for 12 h;
3-Furoic acid (2.8 g, 25 mmoL), diphenyl azidophosphate (6 ml, 27.5 mmoL) and triethylamine (5 mL, 35 mmoL) were added to tert-butanol (50 mL). The mixture was heated to 90° C. and stirred for 12 hours. After cooled to room temperature, aqueous sodium dicarbonate (2 N, 100 mL) was added. The mixture was filtrated, the filter cake was dissolved in ethyl acetate (100 mL), and washed with water (50 mL×3) and saturated brine (50 mL) in sequence, dried over anhydrous sodium sulfate, then filtrated, the filtrate was concentrated under reduced pressure. The residue was purified by silica column chromatography (petroleum ether:ethyl acetate=10:1) to give white solid 30-h (3.2 g, yield: 70percent). LC-MS (ESI): m/z=184 [M+H]+.
54%
for 17 h; Heating / reflux
To a solution of 3-furoic acid (5.0 g, 44.61 mmol) in f-butanol (178 mL) were added diphenylphosphoryl azide (10.7 mL, 49.65 mmol) and triethylamine (8.9 mL, 63.85 mmol) and the mixture heated at reflux for 17 h. The resulting dark solution was cooled to RT, concentrated in vacuo to ~ 50 mL, then poured into an aqueous sat. solution OfNaHCO3 at 0 °C and stirred for 2 h. The resulting precipitate was collected by filtration, washed with a little water, then air dried. The resultant tan solid was purified by column chromatography to give the title compound as a white solid (4.4 g, 54 percent). [M + H]+ 184.0
Reference：
[1] Bulletin de la Societe Chimique de France, 1994, vol. 131, # 4, p. 429 - 433
4
[ 56267-48-2 ]
[ 616-38-6 ]
[ 956034-03-0 ]
Yield
Reaction Conditions
Operation in experiment
83%
Stage #1: With n-butyllithium; N,N,N,N,-tetramethylethylenediamine In tetrahydrofuran at -30 - 0℃; for 1 h; Stage #2: at -30 - 0℃; for 0.75 h;
To a solution of furan-3-yl-carbamic acid tert-butyl ester (4.2 g, 22.93 mmol) in anhydrous THF (160 mL) was added NJfJT JV-tetramethylethylenediamine (4.3 mL, 28.49 mmol) and the resulting orange solution was cooled to -30 °C. n-Butyl lithium (2.5 M in hexanes, 20.0 mL, 50.0 mmol) was added dropwise and the resulting suspension allowed to warm to 0 0C over 1 h. The reaction mixture was cooled to -30 °C and treated with dimethyl carbonate (5.75 mL, 68.24 mmol), then allowed to warm to 0 °C over 45 min. An aqueous solution of HCl (2 M) was added and the mixture was extracted with EtOAc. The organic layer was isolated, dried (MgSO4) and concentrated in vacuo. The resultant residue was purified by column chromatography to give the title compound as a pale yellow solid (4.60 g, 83 percent).1H NMR (300 MHz, CDCl3): δ 1.54 (s, 9 H), 3.92 (s, 3 H), 7.22 (bs, 1 H), 7.38 (s, 1 H) and 8.18 (bs, I H).
51%
Stage #1: With n-butyllithium; N,N,N,N,-tetramethylethylenediamine In tetrahydrofuran; hexanes at -30 - 0℃; for 1 h; Stage #2: at -30 - 20℃; for 1 h;
To a solution of tert-butyl furan-3-ylcarbamate 32 (1 Jg, 1.0 eq) in THF (50 ml) at -30 0C 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 0C 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, 51percent) : MS (Ql) 242 (M)+.
51%
Stage #1: With n-butyllithium; N,N,N,N,-tetramethylethylenediamine In tetrahydrofuran; hexane at -30 - 0℃; for 1 h; Stage #2: at -30 - 20℃; for 1 h; Stage #3: With hydrogenchloride; water In tetrahydrofuran; hexane
To a solution of tert-butyl furan-3-ylcarbamate 32 (1 Jg, 1.0 eq) in THF (50 ml) at -30 0C 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, 51percent) : MS (Ql) 242 (M)+.
49%
Stage #1: With n-butyllithium; N,N,N,N,-tetramethylethylenediamine In tetrahydrofuran; hexanes at -30 - 0℃; for 1 h; Stage #2: at -30 - 0℃; for 0.75 h;
To a solution of tert-butyl furan-3-ylcarbamate (7G) (21 g, 114.65 mmol) in THF (800 mL) was added N,N, N'N'-tetramethylene ethylenediamine (21.5 mL, 142.45 mmol). The resulting orange solution was cooled to -30 °C before treating dropwise with ra-BuLi (1.6 M in hexanes, 157 mL, 250 mmol) and allowed to warm to O °C for 1 h after the addition of "-BuLi. The solution was again cooled to -30 °C and treated with dimethyl carbonate (28.75 mL, 341 mmol), allowed to warm to 0 °C over 45 min. The reaction was quenched with 2M HC1 (400 mL) and extracted with ethyl acetate (800, 600, 400 mL). The combined organic layers were dried over MgS04, concentrated to dryness, and purified by flash column chromatography (silica gel, eluting with hexanes/ethyl acetate 0 to 100percent) to give methyl 3-(tert- butoxycarbonylamino)furan-2-carboxylate (7H) (13.5 g, 49percent) as a light brown oil. NMR (300 MHz, DMSO) δ 8.32 (s, 1H), 7.85 (s, 1H), 7.10 (s, 1H), 3.83 (s, 3H), 1.50 (s, 9H); MS (ES+) 264.1 (M+Na).
25%
Stage #1: With N,N,N,N,-tetramethylethylenediamine In tetrahydrofuran at -40℃; for 0.333333 h; Stage #2: With n-butyllithium In tetrahydrofuran; hexane at -40 - 0℃; for 1.66667 h; Stage #3: at 0 - 20℃; for 1 h;
At −40° C., to a solution of compound 30-h (1.7 g, 9.3 mmoL) in anhydrous THF (50 mL) was added N,N-tetramethylethylenediamine (1.8 mL, 12.1 mmoL), after stirred for 20 minutes, a solution of n-BuLi in n-hexane (2.5 N, 8.4 mL, 21 mmoL) was added dropwise and the reaction temperature was maintained at −40° C. After completion of dropping, the mixture was stirred for further 30 minutes. The mixture was warmed slowly to 0° C., and stirred for another 1 hour, then cooled again to −40° C., stirred for 10 minutes, dimethyl carbonate (2.4 mL, 28 mmoL) was added rapidly to the mixture. The reaction mixture was warmed slowly to room temperature, stirred for another 1 hour. Aqueous hydrochloride solution (2 N, 11 mL) and water (100 mL) were added to quench the reaction, then the mixture was extracted with ethyl acetate (100 mL×3). The organic layers were combined, dried over anhydrous sodium sulfate, then filtrated, and the filtrate was concentrated under reduced pressure. The residue was purified by silica column chromatography (petroleum ether:ethyl acetate=100:1) to give white solid 30-g (0.56 g, yield: 25percent). LC-MS (ESI): m/z=142 [M+H]+.
With diphenyl phosphoryl azide; triethylamine; In toluene; at 20℃;Reflux;
e. To a solution of 3-furoic acid 96 (54.4 g, 485 mmol), triethylamine (105 ml, 753 mmol), tert-butanol (25.2 mL, 786 mmol) in toluene (800 mL) was added dropwise at room temperature over 45 min period diphenyl phosphoryl azide (157.8 mL, 732 mmol). The resulting solution was heated at reflux for 6 h and at room temperature overnight. The reaction was diluted with water (1000 mL) and extracted twice with ethyl acetate (1000 ml). The organic layers were combined washed with water (800 mL), brine (800 mL), decolorized with activated charcoal, dried, filtered and concentrated in vacuo to furnish a brown semisolid. The semisolid was crystallized from dichloromethane (300 mL) and hexanes (600 mL) to furnish tert-butyl furan-3-ylcarbamate 97 (61.5 g, 78%). 1H NMR (300 MHz, CDC13) delta 7.71 (s, IH), 7.30 - 7.24 (m, IH), 6.43 (s, IH), 6.27 (s, IH), 1.75 - 1.32 (s, 9H).
76%
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) delta 7.71 (bs, 1H), 7.27 (m, 1H), 6.27 (bs, 1H), 6.20 (bs, 1H), 1.50 (s, 9H); MS (Q1) 184 (M)+.
76%
3-Furoic acid (5.6Og, 1.0 eq) was dissolved in fert-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) delta 7.71 (bs, IH), 7.27 (m, IH), 6.27 (bs, IH), <n="139"/>6.20 (bs, IH), 1.50 (s, 9H) ; MS (Ql) 184 (M)+.
76%
3-Furoic acid (5.6Og, 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 0C 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) delta 7.71 (bs, IH), 7.27 (m, IH), 6.27 (bs, IH), 6.20 (bs, IH), 1.50 (s, 9H) ; MS (Ql) 184 (M)+.
71%
With diphenyl phosphoryl azide; triethylamine; In toluene; for 6h;Heating / reflux;
Diphenylphosphoryl azide (78.9 mL) was added dropwise to a solution of 3-furoic acid (Aldrich) (27.2 g) in a mixture of toluene (400 mL), triethylamine (52.5 [ML)] and tert- butanol (35.1 [ML).] The solution was heated to reflux for 6 hours, cooled overnight and water added (500 mL). The mixture was extracted into EtOAc (3 x 500 mL) and the combined organics washed with water [(400 ML), BRINE] (400 mL), decolourised over activated charcoal, dried [(MGS04),] and the solvent removed to give 73 g of a brownish solid. Trituration with 1: 1 [DCM/ISOHEXANE] gave the title compound as a white solid (31.5 g, 71%) ; [1H] NMR [(CDC13)] [8 1.] 50 (s, 9H), 6.22 (s, br, 1H), 6.27 (s, 1H), 7.26 (d, 1H), 7.69 (s, br, [1H)] ; MS [M/E] [MU 184.]
70%
With diphenyl phosphoryl azide; triethylamine; at 90℃; for 12h;
3-Furoic acid (2.8 g, 25 mmoL), diphenyl azidophosphate (6 ml, 27.5 mmoL) and triethylamine (5 mL, 35 mmoL) were added to tert-butanol (50 mL). The mixture was heated to 90 C. and stirred for 12 hours. After cooled to room temperature, aqueous sodium dicarbonate (2 N, 100 mL) was added. The mixture was filtrated, the filter cake was dissolved in ethyl acetate (100 mL), and washed with water (50 mL×3) and saturated brine (50 mL) in sequence, dried over anhydrous sodium sulfate, then filtrated, the filtrate was concentrated under reduced pressure. The residue was purified by silica column chromatography (petroleum ether:ethyl acetate=10:1) to give white solid 30-h (3.2 g, yield: 70%). LC-MS (ESI): m/z=184 [M+H]+.
54%
With diphenyl phosphoryl azide; triethylamine; for 17h;Heating / reflux;
To a solution of 3-furoic acid (5.0 g, 44.61 mmol) in f-butanol (178 mL) were added diphenylphosphoryl azide (10.7 mL, 49.65 mmol) and triethylamine (8.9 mL, 63.85 mmol) and the mixture heated at reflux for 17 h. The resulting dark solution was cooled to RT, concentrated in vacuo to ~ 50 mL, then poured into an aqueous sat. solution OfNaHCO3 at 0 C and stirred for 2 h. The resulting precipitate was collected by filtration, washed with a little water, then air dried. The resultant tan solid was purified by column chromatography to give the title compound as a white solid (4.4 g, 54 %). [M + H]+ 184.0
To a solution of furan-3-yl-carbamic acid tert-butyl ester (4.2 g, 22.93 mmol) in anhydrous THF (160 mL) was added NJfJT JV-tetramethylethylenediamine (4.3 mL, 28.49 mmol) and the resulting orange solution was cooled to -30 C. n-Butyl lithium (2.5 M in hexanes, 20.0 mL, 50.0 mmol) was added dropwise and the resulting suspension allowed to warm to 0 0C over 1 h. The reaction mixture was cooled to -30 C and treated with dimethyl carbonate (5.75 mL, 68.24 mmol), then allowed to warm to 0 C over 45 min. An aqueous solution of HCl (2 M) was added and the mixture was extracted with EtOAc. The organic layer was isolated, dried (MgSO4) and concentrated in vacuo. The resultant residue was purified by column chromatography to give the title compound as a pale yellow solid (4.60 g, 83 %).1H NMR (300 MHz, CDCl3): delta 1.54 (s, 9 H), 3.92 (s, 3 H), 7.22 (bs, 1 H), 7.38 (s, 1 H) and 8.18 (bs, I H).
51%
To a solution of <strong>[56267-48-2]tert-butyl furan-3-ylcarbamate</strong> 32 (1 Jg, 1.0 eq) in THF (50 ml) at -30 0C 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 0C 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 (Ql) 242 (M)+.
51%
To a solution of <strong>[56267-48-2]tert-butyl furan-3-ylcarbamate</strong> 32 (1 Jg, 1.0 eq) in THF (50 ml) at -30 0C 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 (Ql) 242 (M)+.
49%
To a solution of <strong>[56267-48-2]tert-butyl furan-3-ylcarbamate</strong> (7G) (21 g, 114.65 mmol) in THF (800 mL) was added N,N, N'N'-tetramethylene ethylenediamine (21.5 mL, 142.45 mmol). The resulting orange solution was cooled to -30 C before treating dropwise with ra-BuLi (1.6 M in hexanes, 157 mL, 250 mmol) and allowed to warm to O C for 1 h after the addition of «-BuLi. The solution was again cooled to -30 C and treated with dimethyl carbonate (28.75 mL, 341 mmol), allowed to warm to 0 C over 45 min. The reaction was quenched with 2M HC1 (400 mL) and extracted with ethyl acetate (800, 600, 400 mL). The combined organic layers were dried over MgS04, concentrated to dryness, and purified by flash column chromatography (silica gel, eluting with hexanes/ethyl acetate 0 to 100%) to give methyl 3-(tert- butoxycarbonylamino)furan-2-carboxylate (7H) (13.5 g, 49%) as a light brown oil. NMR (300 MHz, DMSO) delta 8.32 (s, 1H), 7.85 (s, 1H), 7.10 (s, 1H), 3.83 (s, 3H), 1.50 (s, 9H); MS (ES+) 264.1 (M+Na).
25%
At -40 C., to a solution of compound 30-h (1.7 g, 9.3 mmoL) in anhydrous THF (50 mL) was added N,N-tetramethylethylenediamine (1.8 mL, 12.1 mmoL), after stirred for 20 minutes, a solution of n-BuLi in n-hexane (2.5 N, 8.4 mL, 21 mmoL) was added dropwise and the reaction temperature was maintained at -40 C. After completion of dropping, the mixture was stirred for further 30 minutes. The mixture was warmed slowly to 0 C., and stirred for another 1 hour, then cooled again to -40 C., stirred for 10 minutes, dimethyl carbonate (2.4 mL, 28 mmoL) was added rapidly to the mixture. The reaction mixture was warmed slowly to room temperature, stirred for another 1 hour. Aqueous hydrochloride solution (2 N, 11 mL) and water (100 mL) were added to quench the reaction, then the mixture was extracted with ethyl acetate (100 mL×3). The organic layers were combined, dried over anhydrous sodium sulfate, then filtrated, and the filtrate was concentrated under reduced pressure. The residue was purified by silica column chromatography (petroleum ether:ethyl acetate=100:1) to give white solid 30-g (0.56 g, yield: 25%). LC-MS (ESI): m/z=142 [M+H]+.
3-(tert-butoxycarbonylamino)furan-2-carboxylic acid[ No CAS ]
Yield
Reaction Conditions
Operation in experiment
70%
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 C02 (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 x 100 [ML).] The combined organic phases were washed with ether, acidified by addition of aqueous HCl, and extracted into EtOAc (4 x 250 [ML).] The combined extracts were dried and evaporated to give a pale yellow solid (7. [5G).] This was triturated with cyclohexane to afford the title compound as a white solid (4.80 g, 70%); [1H NMR] (DMSO-d6) [5] 1.46 (s, 9H), 7.05 (s, 1H), 7.76 (s, [1H),] 8.27 (s, [1EI),] 13.36 (s, br, 1H); MS m/e (M-H)-226.
53%
f. To a solution of <strong>[56267-48-2]tert-butyl furan-3-ylcarbamate</strong> 97 (5.49 g, 30 mmol) in THF (60 mL) cooled to -40 0C was added n-butyl lithium (1.6 M, 45 mL, 72 mmol) dropwise. The reaction was stirred at -40 0C for 4 h and quenched into dry CO2 (100 mL) in ether (300 mL). The reaction mixture was poured into water (300 mL) with stirring and the aqueous layer was separated. The aqueous layer was washed with ether (100 mL). The combined organic layer was extracted with water (2 x 100 mL). The aqueous layers were combined acidified with cone. HCl and extracted with ethyl acetate (3 x 200 mL). The ethyl acetate layers were combined dried, filtered and concentrated in vacuo to furnish yellow solid (5.48 g). The yellow solid was triturated with hexanes and solid obtained was collected by filtration to furnish 3-(tert-butoxycarbonylamino)furan-2- carboxylic acid 98 (3.6 g, 53%) as a light yellow solid'H NMR (300 MHz, DMSO) delta 13.23 (s, IH), 8.35 - 8.23 (m, IH), 7.77 (t, J= 10.0, IH), 7.07 (s, IH), 1.53 - 1.40 (m, 9H).
n-BuLi (1.6M, 11.0 mL, 17.6 mmol) was added to a solution of tert-butyl thiophen-3-ylcarbamate (1.59 g, 8.0 mmol) in anhyrous THF (20 mL) at -78 oC. After stirring for 1 hour, allyl bromide (0.73 mL, 8.4 mmol) was added. The reaction was allowed to warm to 0 oC, then quenched with sat. NH4Cl solution. EtOAc was added and the layers separated. The aqueous was extracted with EtOAc, and the combined organics were dried over Na2SO4 and concentrated to give the C-alkylated product as a white solid (1.30 g, 68%). The residue (1.2 g, 5.0 mmol) was dissolved in DMF (12 mL) and cooled in an ice-bath. NaH (60% disp. 667 mg, 6.0 mmol) was added and the reaction was stirred for 15 min before allyl bromide (0.48 mL, 5.5 mmol) was added and the reaction was stirred for a further 30 min. Water and EtOAc were added and the layers separated. The organic was dried over Na2SO4 and concentrated. The residue was purified by silica gel chromatography [heptane/EtOAc, 95:5 - 4:1] to give the product as a colourless oil (1.20 g, 86%)
tert-butyl (2-(2,2,2-trichloroacetyl)furan-3-yl)carbamate[ No CAS ]
Yield
Reaction Conditions
Operation in experiment
73 g
With triethylamine; In dichloromethane; at 0 - 20℃; for 2h;
Tert-butylfuran-3-ylcarbamate (formula 2A; see patent publication no. WO2008073785A2) 40 g (218 mmol) was dissolved in dichloromethane (MC) After dilution with 400 ml, to this was added 26.5 g (262 mmol) of triethylamine. After the reaction was cooled to 0 C, a solution of 29.2 ml (262 mmol) of trichloroacetyl chloride (Formula 3A) in 200 ml of dichloromethane was slowly added and stirred at room temperature for 2 hours. After completion of the reaction, the reaction mixture was cooled to 0 , adjusted to pH 7 with a saturated aqueous sodium carbonate solution, and washed sequentially with distilled water and saturated brine. The obtained organic layer was dried over anhydrous sodium sulfate, filtered under reduced pressure and distilled under reduced pressure to obtain a solid, which was dried under reduced pressure to obtain 73 g of the title compound (yield: 100%).
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