benzyl 2-fluorobenzoate

反応条件: temp:0.00; pressure:0.00; stir:

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: Benzyl alcohol (4.05 mL, 39.1 mmol) was added slowly to a stirring solution of 4-fluorobenzoic acid (5.00 g, 35.7 mmol), 4-(dimethylamino)pyridine (432 mg, 3.53 mmol), and 1,3-dicyclohexylcarbodiimide (8.15 g, 39.5 mmol) in anhydrous CH2Cl2 at room temperature under an argon atmosphere. After 18 h the reaction was worked up according to procedures as outlined for the synthesis of 16. Flash chromatographic purification over silica (10% EtOAc in hexanes) afforded 17 as a clear, colorless liquid (7.75 g, 94%). 1H-NMR (500 MHz, CDCl3) δ 5.35 (s, 2H), 7.06-14 (m, 2H), 7.32-7.41 (m, 3H), 7.41-7.47 (m, 2H), 8.06-8.12 (m, 2H); 13C-NMR (125 MHz, CDCl3) δ 66.84, 115.5 (d, JC-F=22.0 Hz), 126.4 (d, JC-F=2.9 Hz), 128.2, 128.3, 128.6, 132.3 (d, JC-F=9.6 Hz), 135.9, 165.5, 165.8 (d, JC-F=253 Hz); GC-MS 230 m/z [M]+, C14H11OF2 requires 230. 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: Benzyl alcohol (2.60 mL, 25.1 mmol) was added slowly to a stirring solution of 2-fluorobenzoic acid (2.92 g, 20.8 mmol), 4-(dimethylamino)pyridine (251 mg, 2.05 mmol), and 1,3-dicyclohexylcarbodiimide (5.16 g, 25.0 mmol) in anhydrous CH2Cl2 at room temperature under an Ar atmosphere. After 18 h the precipitate was filtered off and washed with CH2Cl2, and the filtrate was concentrated with silica to a powder. Flash chromatographic purification over silica (10% to 20% gradient EtOAc in hexanes) afforded 16 as a clear, colorless liquid (4.20 g, 88%). 1H-NMR (500 MHz, CDCl3) δ 5.39 (s, 2H), 7.14 (ddd, J=1.1, 8.4, 9.5 Hz, 1H), 7.20 (dt, J=1.1, 7.7 Hz, 1H), 7.31-7.36 (m, 1H), 7.37-7.41 (m, 2H), 7.44-7.48 (m, 2H), 7.49-7.55 (m, 1H), 7.96 (dt, J=1.8, 7.3 Hz); 13C-NMR (125 MHz, CDCl3) δ 66.93, 117.0 (d, JC-F=22.1 Hz), 118.7 (d, JC-F=9.6 Hz), 124.0 (d, JC-F=3.8 Hz), 128.1, 128.2, 128.6, 132.2, 134.6 (d, JC-F=9.6 Hz), 135.7, 162.1 (d, JC-F=260 Hz), 164.2 (d, JC-F=3.8 Hz); GC-MS 230 m/z [M]+, C14H11OF2 requires 230. After 18 h the precipitate was filtered off washed with CH2Cl2 the filtrate was concentrated with silica to a powder Flash chromatographic purification over silica (10% to 20% gradient EtOAc in hexanes)

反応条件: temp:0.00; pressure:0.00; stir:

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: Benzyl alcohol (4.05 mL, 39.1 mmol) was added slowly to a stirring solution of 4-fluorobenzoic acid (5.00 g, 35.7 mmol), 4-(dimethylamino)pyridine (432 mg, 3.53 mmol), and 1,3-dicyclohexylcarbodiimide (8.15 g, 39.5 mmol) in anhydrous CH2Cl2 at room temperature under an argon atmosphere. After 18 h the reaction was worked up according to procedures as outlined for the synthesis of 16. Flash chromatographic purification over silica (10% EtOAc in hexanes) afforded 17 as a clear, colorless liquid (7.75 g, 94%). 1H-NMR (500 MHz, CDCl3) δ 5.35 (s, 2H), 7.06-14 (m, 2H), 7.32-7.41 (m, 3H), 7.41-7.47 (m, 2H), 8.06-8.12 (m, 2H); 13C-NMR (125 MHz, CDCl3) δ 66.84, 115.5 (d, JC-F=22.0 Hz), 126.4 (d, JC-F=2.9 Hz), 128.2, 128.3, 128.6, 132.3 (d, JC-F=9.6 Hz), 135.9, 165.5, 165.8 (d, JC-F=253 Hz); GC-MS 230 m/z [M]+, C14H11OF2 requires 230. 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: Benzyl alcohol (2.60 mL, 25.1 mmol) was added slowly to a stirring solution of 2-fluorobenzoic acid (2.92 g, 20.8 mmol), 4-(dimethylamino)pyridine (251 mg, 2.05 mmol), and 1,3-dicyclohexylcarbodiimide (5.16 g, 25.0 mmol) in anhydrous CH2Cl2 at room temperature under an Ar atmosphere. After 18 h the precipitate was filtered off and washed with CH2Cl2, and the filtrate was concentrated with silica to a powder. Flash chromatographic purification over silica (10% to 20% gradient EtOAc in hexanes) afforded 16 as a clear, colorless liquid (4.20 g, 88%). 1H-NMR (500 MHz, CDCl3) δ 5.39 (s, 2H), 7.14 (ddd, J=1.1, 8.4, 9.5 Hz, 1H), 7.20 (dt, J=1.1, 7.7 Hz, 1H), 7.31-7.36 (m, 1H), 7.37-7.41 (m, 2H), 7.44-7.48 (m, 2H), 7.49-7.55 (m, 1H), 7.96 (dt, J=1.8, 7.3 Hz); 13C-NMR (125 MHz, CDCl3) δ 66.93, 117.0 (d, JC-F=22.1 Hz), 118.7 (d, JC-F=9.6 Hz), 124.0 (d, JC-F=3.8 Hz), 128.1, 128.2, 128.6, 132.2, 134.6 (d, JC-F=9.6 Hz), 135.7, 162.1 (d, JC-F=260 Hz), 164.2 (d, JC-F=3.8 Hz); GC-MS 230 m/z [M]+, C14H11OF2 requires 230. After 18 h the precipitate was filtered off washed with CH2Cl2 the filtrate was concentrated with silica to a powder Flash chromatographic purification over silica (10% to 20% gradient EtOAc in hexanes)