benzyl N-but-3-enylcarbamate

反応条件: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: Bromine (11 g, 68 mmol) was added to a mixture of benzyl but-3-en-1-ylcarbamate (7 g, 34 mmol) in DCM at room temperature under N2. The mixture was stirred at room temperature for 4 hours. The mixture was diluted with water and extracted with DCM. The organic layer was dried over anhydrous sodium sulfate, filtered, and concentrated under reduced pressure. The residue was purified by silica gel column chromatography (petroleum ether/EtOAc) to afford 6-(bromomethyl)-1,3-oxazinan-2-one. 1H NMR (400 MHz, CDCl3) δ 6.14 (s, 1H), 4.49-4.45 (m, 1H), 3.59-3.56 (m, 1H), 3.46-3.39 (m, 3H), 2.24-2.20 (m, 1H), 1.95-1.89 (m, 1H). extracted with DCM The organic layer was dried over anhydrous sodium sulfate filtered concentrated under reduced pressure The residue was purified by silica gel column chromatography (petroleum ether/EtOAc)

反応条件: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: Benzyl chloroformate (38 g, 0.22 mol) was added at 0° C. over 15 minutes to a mixture of but-3-en-1-amine (10 g, 0.14 mol) and sodium bicarbonate (35 g, 0.52 mol) in DCM (500 mL) and water (40 mL). The mixture was diluted with water and extracted with DCM. The organic layer was dried over anhydrous sodium sulfate, filtered, and concentrated under reduced pressure. The residue was purified by silica gel column chromatography (petroleum ether/EtOAc) to afford benzyl but-3-en-1-ylcarbamate. MS ESI calc'd. for C12H16NO2 [M+H]+ 206. found 206. 1H NMR (400 MHz, CDCl3) δ 7.36-7.30 (m, 5H), 5.80-5.70 (m, 1H), 5.11-5.01 (m, 4H), 3.79-3.25 (m, 2H), 2.29-2.24 (m, 2H). extracted with DCM The organic layer was dried over anhydrous sodium sulfate filtered concentrated under reduced pressure The residue was purified by silica gel column chromatography (petroleum ether/EtOAc)

反応条件: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: To a solution of but-3-enyl-carbamic acid benzyl ester (prepared according to Heterocycles (2006), 67(2), 549-554; 21.5 g, 105 mmol) in chloroform (380 mL) was added, dropwise over a period of 1 h, a solution of MCPBA (28.3 g, 1.1 eq.) in chloroform (270 mL) at 10° C. Stirring was continued for 20 h at rt. The reaction mixture was filtered and 10% sodium sulfite solution was added to the filtrate (until starch-iodide paper test was negative). The mixture was washed with 5% Na2CO3 and brine. The org. layer was dried over MgSO4 and concentrated to afford the title intermediate as a colourless liquid (21.6 g, 93% yield). at 10° C The reaction mixture was filtered 10% sodium sulfite solution was added to the filtrate (until starch-iodide paper test was negative) The mixture was washed with 5% Na2CO3 and brine layer was dried over MgSO4 concentrated

反応条件: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: A solution of but-3-enyl-carbamic acid benzyl ester (3.06 g, 14.0 mmol, 1 eq) in anhydrous toluene (40 mL) was cooled under argon to 0-5° C. 9-BBN (0.50 M, solution in THF; 30.8 mL, 1504 mmol, 1.1 eq.) was added dropwise, the mixture was stirred and allowed to reach room temperature. After 24 h, 1N NaOH/H2O (23.8 mL, 23.8 mmol, 1.7 eq.) was added, followed by 2-bromo-4-trifluoromethyl-pyridine (3.16 g, 14.0 mmol, 1 eq.) and toluene (25 mL). The resulting mixture was degassed and Pd(PPh3)4 (0.89 g, 0.70 mmol, 0.05 eq.) was added. The mixture was rapidly stirred under argon at 60° C. for 24 h, and then it was cooled to room temperature. Afterwards, the mixture was partitioned between EtOAc (100 mL) and brine (100 mL). The organic phase was washed with brine (100 mL), dried over Na2SO4, filtered and concentrated. The crude product was purified by flash chromatography on silica gel (0-50% EtOAc in Heptane) to afford 2 as colorless oil (5.1 g, 99%). to reach room temperature The resulting mixture was degassed The mixture was rapidly stirred under argon at 60° C. for 24 h Afterwards, the mixture was partitioned between EtOAc (100 mL) and brine (100 mL) The organic phase was washed with brine (100 mL) dried over Na2SO4 filtered concentrated The crude product was purified by flash chromatography on silica gel (0-50% EtOAc in Heptane)

反応条件: temp:60.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: A solution of but-3-enyl-carbamic acid benzyl ester (5.00 g, 24.36 mmol, 1 eq) in anhydrous toluene (60 mL) was cooled under argon to 0-5° C. 9-BBN (0.50 M, solution in THF; 54.6 mL, 26.80 mmol, 1.1 eq.) was added dropwise, and the mixture was allowed to reach room temperature. After 24 h, the resulting solution was added dropwise at room temperature to a mixture of 2a (7.03 g, 24.36 mmol, 1 eq.), 1N NaOH/H2O (40 mL, 40 mmol, 1.6 eq.), and toluene (20 mL). The mixture was then degassed with argon and Pd(PPh3)4 (1.13 g, 0.98 mmol, 0.04 eq.) was added. The mixture was rapidly stirred under argon at 60° C. for 24 h, before cooling to room temperature. The mixture was partitioned between EtOAc (150 mL) and brine (150 mL). The organic phase was washed with brine (200 mL), dried over Na2SO4, filtered and concentrated. The crude product was purified by flash chromatography on silica gel (0-50% EtOAc in Heptane) to afford 3a as a colorless oil (3.54 g, 35%). to reach room temperature was added before cooling to room temperature The mixture was partitioned between EtOAc (150 mL) and brine (150 mL) The organic phase was washed with brine (200 mL) dried over Na2SO4 filtered concentrated The crude product was purified by flash chromatography on silica gel (0-50% EtOAc in Heptane)

反応条件: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: Bromine (11 g, 68 mmol) was added to a mixture of benzyl but-3-en-1-ylcarbamate (7 g, 34 mmol) in DCM at room temperature under N2. The mixture was stirred at room temperature for 4 hours. The mixture was diluted with water and extracted with DCM. The organic layer was dried over anhydrous sodium sulfate, filtered, and concentrated under reduced pressure. The residue was purified by silica gel column chromatography (petroleum ether/EtOAc) to afford 6-(bromomethyl)-1,3-oxazinan-2-one. 1H NMR (400 MHz, CDCl3) δ 6.14 (s, 1H), 4.49-4.45 (m, 1H), 3.59-3.56 (m, 1H), 3.46-3.39 (m, 3H), 2.24-2.20 (m, 1H), 1.95-1.89 (m, 1H). extracted with DCM The organic layer was dried over anhydrous sodium sulfate filtered concentrated under reduced pressure The residue was purified by silica gel column chromatography (petroleum ether/EtOAc)

反応条件: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: Benzyl chloroformate (38 g, 0.22 mol) was added at 0° C. over 15 minutes to a mixture of but-3-en-1-amine (10 g, 0.14 mol) and sodium bicarbonate (35 g, 0.52 mol) in DCM (500 mL) and water (40 mL). The mixture was diluted with water and extracted with DCM. The organic layer was dried over anhydrous sodium sulfate, filtered, and concentrated under reduced pressure. The residue was purified by silica gel column chromatography (petroleum ether/EtOAc) to afford benzyl but-3-en-1-ylcarbamate. MS ESI calc'd. for C12H16NO2 [M+H]+ 206. found 206. 1H NMR (400 MHz, CDCl3) δ 7.36-7.30 (m, 5H), 5.80-5.70 (m, 1H), 5.11-5.01 (m, 4H), 3.79-3.25 (m, 2H), 2.29-2.24 (m, 2H). extracted with DCM The organic layer was dried over anhydrous sodium sulfate filtered concentrated under reduced pressure The residue was purified by silica gel column chromatography (petroleum ether/EtOAc)