ethyl N-hydroxyethanimidate

反応条件: temp:0.00; pressure:0.00; stir:

反応条件: temp:0.00; pressure:0.00; stir:

反応条件: temp:0.00; pressure:0.00; stir:

反応条件: temp:20.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: To a suspension of 23.8 g (0.42 mol) of potassium hydroxide in 220 ml of N,N-dimethylformamide at 10° C. are added 40.0 g of ethyl N-hydroxyethaneimidoate (0.39 mol) (compound VI: R3═C2H5; R4═CH3). A solution of 55.6 g of 4-chloronitrobenzene (0.35 mol) (compound V: Hal=Cl) (55.6 g) in N,N-dimethylformamide is then added slowly, at 10° C. The mixture is stirred for 24 hours at 20° C. and 1 L of water is then added. The precipitate is filtered off and the solid is washed with water and oven-dried at 30° C. under vacuum to constant weight. The precipitate is filtered off the solid is washed with water oven-dried at 30° C. under vacuum to constant weight

反応条件: temp:0.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: Ethyl N-hydroxyacetimidate(0.23 g, 0.002 mol) was added dropwise to a suspension of sodium hydride(008 g, 0.002 mol) in tetrahydrofuran(5 ml) with stirring at 0° C. 2-Chloro-3-[4-chloro-2-fluoro-5-(2-nitrophenoxy)phenyl]-6-trifluoromethyl-4(3H)-pyrimidinone(0.93 g, 0.002 mol) was added to the mixture at 0° C., and the mixture was stirred at 0° C. for 3 hours. The reaction mixture was poured into water and extracted with ethyl acetate. The ethyl acetate solution was concentrated and purified by column chromatography on silica gel(20% ethyl acetate/hexane) to give compound II-1 (0.90 g, yield 85%) as a white solid, m.p.152-155° C. the mixture was stirred at 0° C. for 3 hours extracted with ethyl acetate The ethyl acetate solution was concentrated purified by column chromatography on silica gel(20% ethyl acetate/hexane) to give compound II-1 (0.90 g, yield 85%) as a white solid, m.p.152-155° C.

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

実験手順: To a stirring solution of ethyl-N-hydroxyacetimidate (3.79 g, 36.8 mmol) in anhydrous DMF (150 mL) under Ar was added tBuOK (4.09 g, 36.4 mmol) all at once. After 40 min benzyl-4-fluorobenzoate 17 (7.63 g, 17.9 mmol) was added and the reaction was stirred at room temperature. After 4 h the reaction was diluted with H2O (500 mL), extracted with EtOAc (4×100 mL), and the combined organics were washed with H2O (2×100 mL), dried over Na2SO4, filtered, and concentrated. Flash chromatographic purification over silica (5-10% gradient EtOAc in hexanes) afforded 19 as a clear syrup (6.02 g, 58%). 1H-NMR (500 MHz, CDCl3) δ 1.36 (t, J=7.0 Hz, 3H), 2.12 (s, 3H), 4.20 (q, J=7.0 Hz, 2H), 5.34 (s, 2H), 7.15-7.19 (m, 2H), 7.31-7.35 (m, 2H), 7.36-7.41 (m, 2H), 7.42-7.36 (m, 2H), 8.00-8.14 (m, 2H); 13C-NMR (125 MHz, CDCl3) δ 14.3, 14.4, 63.1, 66.4, 113.4, 122.9, 128.1, 128.1, 128.6, 131.5, 136.3, 163.5, 166.3, 166.4; GC-MS 228 m/z [M-85]+, benzyl-4-hydroxybenzoate C14H12O3 requires 228. extracted with EtOAc (4×100 mL) the combined organics were washed with H2O (2×100 mL) dried over Na2SO4 filtered concentrated Flash chromatographic purification over silica (5-10% gradient EtOAc in hexanes)

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

実験手順: To a stirring solution of ethyl-N-hydroxyacetimidate (2.06 g, 20.0 mmol) in anhydrous DMF (60 mL) under Ar was added tBuOK (2.21 g, 19.7 mmol) all at once. After 30 min benzyl-2-fluorobenzoate 16 (4.13 g, 17.9 mmol) was added as a solution in DMF (20 mL) and the reaction was stirred at room temperature. After 3 h the reaction was diluted with H2O (400 mL), extracted with EtOAc (3×100 mL), and the combined organics were washed with H2O (3×50 mL) and brine (50 mL), dried over Na2SO4, filtered, and concentrated. Flash chromatographic purification over silica (5-10% gradient EtOAc in hexanes) afforded 18 as a clear syrup (3.61 g, 64%). 1H-NMR (500 MHz, CDCl3) δ 1.34 (t, J=7.0 Hz, 3H), 2.00 (s, 3H), 4.18 (q, J=7.0 Hz, 2H), 5.34 (s, 2H), 6.96 (dt, J=1.1, 7.7 Hz, 1H), 7.30-7.35 (m, 1H), 7.35-7.39 (m, 2H), 7.42-7.48 (m, 3H), 7.55 (dd, J=1.1, 8.4 Hz, 1H), 7.90 (dd, J=1.8, 7.7 Hz, 1H); 13C-NMR (125 MHz, CDCl3) δ 14.4, 14.5, 63.1, 66.6, 114.5, 117.0, 120.4, 128.2, 128.4, 128.5, 131.7, 133.8, 136.1, 159.5, 165.8, 166.7; GC-MS 313 m/z[M]+, C18H19NO4 requires 313, 228 m/z [M-85]+, benzyl-2-hydroxybenzoate C14H12O3 requires 228. extracted with EtOAc (3×100 mL) the combined organics were washed with H2O (3×50 mL) and brine (50 mL) dried over Na2SO4 filtered concentrated Flash chromatographic purification over silica (5-10% gradient EtOAc in hexanes)

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

実験手順: Prepared using a procedure adapted from Miyazawa et al. (Miyazawa, E.; et al. Org. Prep. Proced. Int. 1997, 29, 594-600) tBuOK (0.78 g, 6.7 mmol) was added to a stirring solution of ethyl-N-hydroxyacetimidate (1.00 g, 6.06 mmol) in anhydrous DMF (6 mL) at 0° C. under an Ar atmosphere. After tBuOK addition was completed the reaction was stirred at room temperature. After 30 min 2-fluorobenzotrifluoride (1.29 mL, 6.06 mmol) was added and the reaction was heated at 80° C. for 2 h. Upon cooling the reaction mixture was diluted with ice water (100 mL) and extracted with EtOAc (3×40 mL). The combined organic layers were washed with brine (2×50 mL), dried with MgSO4, and concentrated to afford a dark oil. Flash chromatographic purification over silica (10% EtOAc in hexanes) afforded 15 as a clear liquid (1.33 g, 89%). 1H-NMR (500 MHz, CDCl3) δ 1.36 (t, J=7.1 Hz, 3H), 2.15 (s, 3H), 4.20 (q, J=7.1 Hz, 2H), 6.99 (apparent t, J=7.5 Hz, 1H), 7.47 (apparent dt, J=7.9 Hz, 1H), 7.52-7.57 (m, 2H); 13C-NMR (125 MHz, CDCl3) δ 14.3, 14.5, 63.2, 114.2, 116.2 (q, JC-F=31 Hz), 120.3, 123.7 (q, JC-F=272 Hz), 126.4 (q, JC-F=4.8 Hz), 133.2, 157.2 (q, JC-F=1.9 Hz), 167.1; LC-MS 248 m/z[MH]+, C11H13F3NO2 requires 248. Prepared the reaction was heated at 80° C. for 2 h Upon cooling the reaction mixture extracted with EtOAc (3×40 mL) The combined organic layers were washed with brine (2×50 mL) dried with MgSO4 concentrated to afford a dark oil Flash chromatographic purification over silica (10% EtOAc in hexanes)

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

実験手順: Prepared using a procedure adapted from Miyazawa et al. (Miyazawa, E.; et al. Org. Prep. Proced. Int. 1997, 29, 594-600) tBuOK (0.78 g, 6.7 mmol) was added to a stirring solution of ethyl-N-hydroxyacetimidate (1.00 g, 6.06 mmol) in anhydrous DMF (6 mL) at 0° C. under an Ar atmosphere. After tBuOK addition was completed the reaction was stirred at room temperature. After 30 min 2-fluorobenzotrifluoride (1.29 mL, 6.06 mmol) was added and the reaction was heated at 80° C. for 2 h. Upon cooling the reaction mixture was diluted with ice water (100 mL) and extracted with EtOAc (3×40 mL). The combined organic layers were washed with brine (2×50 mL), dried with MgSO4, and concentrated to afford a dark oil. Flash chromatographic purification over silica (10% EtOAc in hexanes) afforded 15 as a clear liquid (1.33 g, 89%). 1H-NMR (500 MHz, CDCl3) δ 1.36 (t, J=7.1 Hz, 3H), 2.15 (s, 3H), 4.20 (q, J=7.1 Hz, 2H), 6.99 (apparent t, J=7.5 Hz, 1H), 7.47 (apparent dt, J=7.9 Hz, 1H), 7.52-7.57 (m, 2H); 13C-NMR (125 MHz, CDCl3) δ 14.3, 14.5, 63.2, 114.2, 116.2 (q, JC-F=31 Hz), 120.3, 123.7 (q, JC-F=272 Hz), 126.4 (q, JC-F=4.8 Hz), 133.2, 157.2 (q, JC-F=1.9 Hz), 167.1; LC-MS 248 m/z[MH]+, C11H13F3NO2 requires 248. Prepared the reaction was heated at 80° C. for 2 h Upon cooling the reaction mixture extracted with EtOAc (3×40 mL) The combined organic layers were washed with brine (2×50 mL) dried with MgSO4 concentrated to afford a dark oil Flash chromatographic purification over silica (10% EtOAc in hexanes)

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

実験手順: To a solution of 5.0 g (0.05 m) of ethyl N-hydroxyacetimidate and 8.5 g (0.05 m) of N-chloroacetyl-N-methyl-carbamoyl chloride dissolved in 75 ml of toluene was added 5.05 g (0.05 m) of triethylamine. After stirring for 2 hours the reaction mixture was filtered through a bed of Celite. The filtrate was concentrated under reduced pressure to afford 10.3 g of a light yellow crystalline solid. m.p. 69°-71° C. was filtered through a bed of Celite The filtrate was concentrated under reduced pressure

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

実験手順: To a solution of 5.0 g (0.05 m) of ethyl N-hydroxyacetimidate and 8.5 g (0.05 m) of N-chloroacetyl-N-methyl-carbamoyl chloride dissolved in 75 ml of toluene was added 5.05 g (0.05 m) of triethylamine. After stirring for 2 hours the reaction mixture was filtered through a bed of Celite. The filtrate was concentrated under reduced pressure to afford 10.3 g of a light yellow crystalline solid. m.p. 69°-71° C. was filtered through a bed of Celite The filtrate was concentrated under reduced pressure

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

実験手順: To a solution of 5.0 g (0.05 m) of ethyl N-hydroxyacetimidate and 8.5 g (0.05 m) of N-chloroacetyl-N-methyl-carbamoyl chloride dissolved in 75 ml of toluene was added 5.05 g (0.05 m) of triethylamine. After stirring for 2 hours the reaction mixture was filtered through a bed of Celite. The filtrate was concentrated under reduced pressure to afford 10.3 g of a light yellow crystalline solid. m.p. 69°-71° C. was filtered through a bed of Celite The filtrate was concentrated under reduced pressure