ethyl (E)-3-(4-bromophenyl)prop-2-enoate

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

実験手順: The colourless solid (E)-3-(4-bromo-phenyl)-prop-2-en-1-ol was prepared by DIBAL-H reduction of (E)-ethyl 3-(4-bromo-phenyl)-acrylate (example 71a) as described for example 52b.

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

実験手順: The colourless solid (E)-ethyl 3-(3′,5′-dichloro-biphenyl-4-yl)-acrylate was prepared from (E)-ethyl 3-(4-bromo-phenyl)-acrylate (example 71a) and 3,5-dichlorobenzene boronic acid by a procedure analogous to that described in example 52a.

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

実験手順: The colourless solid (E)-ethyl 3-(3′,5′-dichloro-biphenyl-4-yl)-acrylate was prepared from (E)-ethyl 3-(4-bromo-phenyl)-acrylate (example 71a) and 3,5-dichlorobenzene boronic acid by a procedure analogous to that described in example 52a.

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

実験手順: The title compound was prepared from (E)-3-(4-bromo-phenyl)-acrylic acid ethyl ester and 2,3-dichlorobenzene boronic acid by a sequence analogous to that described in example 52a-c.

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

実験手順: (E)-3-(4-Bromo-phenyl)-acrylic acid ethyl ester (450 mg, 2.0 mmol) was reacted with 5-isopropyl-2-methoxy-benzene boronic acid (776 mg, 4.0 mmol) by a procedure described in example 52 a, to give (E)-3-(5′-Isopropyl-2′-methoxy-biphenyl-4-yl)-acrylic acid ethyl ester.

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

実験手順: To a solution of E-3-(4-bromo-phenyl)-acrylic acid ethyl ester and Pd(OAc)2 (0.05 eq.) in THF (0.2M) was added portionwise CH2N2 until the reaction was completed. NMR of aliquots monitored the reaction. The resulting mixture was concentrated and filtered on celite to afford the title compound as an oil. the reaction The resulting mixture was concentrated filtered on celite

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

実験手順: 173 mg (0.15 mmol) of tetrakistriphenylphosphine palladium and 4.4 mL (8.8 mmol) of a 2M sodium carbonate solution is added at ambient temperature to a solution of 1.124 g (4.04 mmol) of ethyl (E)-3-(4-bromophenyl)acrylate in 50 mL of dioxane. 0.689 g (4.404 mmol) of 4-chlorophenylboric acid dissolved in 10 mL of methanol is added to this reaction mixture and refluxed for 5 hours. The reaction mixture is evaporated down, the residue is taken up in dichloromethane, and extracted with water. The organic phase is dried over sodium sulfate. The purification is carried out by column chromatography on silica gel (eluant: petroleum ether/ethyl acetate (9:1)). Yield: 0.94 g (74.4% of theory); C17H15ClO2 (M=286.76); calc.: molecular ion peak (M+H)+: 287/289; found: molecular ion peak (M+H)+: 287/289; Rf value: 0.44 (silica gel, petroleum ether/ethyl acetate (40:10)). is added to this reaction mixture refluxed for 5 hours The reaction mixture is evaporated down extracted with water The organic phase is dried over sodium sulfate The purification

反応条件: temp:-78.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: To a solution of (E)-ethyl 3-(4-bromophenyl)acrylate (25 g, 96 mmol) in DCM (300 ml) under nitrogen and cooled to −78° C. was added dropwise DIBAL-H (240 ml, 1M in DCM, 240 mmol) in about 20 minutes. The mixture was stirred at −78° C. for 2 hours. Then, the dry ice bath was removed. The reaction was diluted with DCM (500 mL), quenched with HCl (1N), and partitioned. The combined organic phases were washed with H2O, dried and concentrated under reduced pressure to provide the title compound. 1H NMR (300 MHz, CDCl3): δ 1.43 (t, J=6 Hz, 1H), 4.32 (t, J=4.5 Hz, 2H), 6.37 (dt, J=16.5 Hz, J=6 Hz, 1H), 6.57 (d, J=15 Hz, 1H), 7.25 (d, J=9 Hz, 2H), 7.45 (d, J=9 Hz, 2H). MS (DCI—NH3) m/z 214 (M+H)+. Then, the dry ice bath was removed The reaction was diluted with DCM (500 mL) quenched with HCl (1N) partitioned The combined organic phases were washed with H2O dried 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 vigorously stirring mixture of (CH3)3S(I)O (7.76 g, 35.3 mmol) in DMSO (75 mL) was added NaH (0.972 g, 36.5 mmol) in small portions over 5 min. Following complete addition, the reaction was left to stir for 10 min before the rapid dropwise addition of ethyl trans-4-bromocinnamate (2.21 mL, 11.8 mmol), which is commercially available from, for example, Sigma-Aldrich. After 3 h the reaction was partitioned between EtOAc (100 mL) and H2O (200 mL). The aq. phase washed with EtOAc (2×75 mL) wherein the combined organics were washed with H2O (2×50 mL), brine (50 mL), dried over MgSO4, filtered and concentrated under reduced pressure. The resulting solid was absorbed onto Celite® and subjected to flash chromatography (SiO2-40 g; gradient elution: 5% EtOAc/Hexane isocratic for 3 min then 5-30% EtOAc/Hexane over 20 min at 40 mL/min to afford 1.48 g 13Ai as a white solid (46.7% yield). 1H NMR (500 MHz, CDCl3) δ 7.46-7.33 (m, 2H), 6.97 (d, J=8.6 Hz, 2H), 4.17 (q, J=7.2 Hz, 2H), 2.47 (ddd, J=9.2, 6.4, 4.3 Hz, 1H), 1.86 (ddd, J=8.5, 5.4, 4.2 Hz, 1H), 1.59 (dt, J=9.5, 4.8 Hz, 1H), 1.35-1.18 (m, 4H). addition the reaction was left After 3 h the reaction was partitioned between EtOAc (100 mL) and H2O (200 mL) The aq. phase washed with EtOAc (2×75 mL) wherein the combined organics were washed with H2O (2×50 mL), brine (50 mL) dried over MgSO4 filtered concentrated under reduced pressure The resulting solid was absorbed onto Celite® gradient elution

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

実験手順: To a vigorously stirring mixture of (CH3)3S(I)O (7.76 g, 35.3 mmol) in DMSO (75 mL) was added NaH (0.972 g, 36.5 mmol) in small portions over 5 min. Following complete addition, the reaction was left to stir for 10 min before the rapid dropwise addition of ethyl trans-4-bromocinnamate (2.21 mL, 11.8 mmol), which is commercially available from, for example, Sigma-Aldrich. After 3 h the reaction was partitioned between EtOAc (100 mL) and H2O (200 mL). The aq. phase washed with EtOAc (2×75 mL) wherein the combined organics were washed with H2O (2×50 mL), brine (50 mL), dried over MgSO4, filtered and concentrated under reduced pressure. The resulting solid was absorbed onto Celite® and subjected to flash chromatography (SiO2—40 g; gradient elution: 5% EtOAc/Hexane isocratic for 3 min then 5-30% EtOAc/Hexane over 20 min at 40 mL/min to afford 1.48 g 13Ai as a white solid (46.7% yield). 1H NMR (500 MHz, CDCl3) δ 7.46-7.33 (m, 2H), 6.97 (d, J=8.6 Hz, 2H), 4.17 (q, J=7.2 Hz, 2H), 2.47 (ddd, J=9.2, 6.4, 4.3 Hz, 1H), 1.86 (ddd, J=8.5, 5.4, 4.2 Hz, 1H), 1.59 (dt, J=9.5, 4.8 Hz, 1H), 1.35-1.18 (m, 4H). addition the reaction was left After 3 h the reaction was partitioned between EtOAc (100 mL) and H2O (200 mL) The aq. phase washed with EtOAc (2×75 mL) wherein the combined organics were washed with H2O (2×50 mL), brine (50 mL) dried over MgSO4 filtered concentrated under reduced pressure The resulting solid was absorbed onto Celite® gradient elution

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

実験手順: To a vigorously stirring mixture of (CH3)3S(I)O (7.76 g, 35.3 mmol) in DMSO (75 mL) was added NaH (0.972 g, 36.5 mmol) in small portions over 5 min. Following complete addition, the reaction was left to stir for 10 min before the rapid dropwise addition of ethyl trans-4-bromocinnamate (2.21 mL, 11.8 mmol), which is commercially available from, for example, Sigma-Aldrich. After 3 h the reaction was partitioned between EtOAc (100 mL) and H2O (200 mL). The aq. phase washed with EtOAc (2×75 mL) wherein the combined organics were washed with H2O (2×50 mL), brine (50 mL), dried over MgSO4, filtered and concentrated under reduced pressure. The resulting solid was absorbed onto Celite® and subjected to flash chromatography (SiO2—40 g; gradient elution: 5% EtOAc/Hexane isocratic for 3 min then 5-30% EtOAc/Hexane over 20 min at 40 mL/min to afford 1.48 g 13Ai as a white solid (46.7% yield). 1H NMR (500 MHz, CDCl3) δ 7.46-7.33 (m, 2H), 6.97 (d, J=8.6 Hz, 2H), 4.17 (q, J=7.2 Hz, 2H), 2.47 (ddd, J=9.2, 6.4, 4.3 Hz, 1H), 1.86 (ddd, J=8.5, 5.4, 4.2 Hz, 1H), 1.59 (dt, J=9.5, 4.8 Hz, 1H), 1.35-1.18 (m, 4H). addition the reaction was left After 3 h the reaction was partitioned between EtOAc (100 mL) and H2O (200 mL) The aq. phase washed with EtOAc (2×75 mL) wherein the combined organics were washed with H2O (2×50 mL), brine (50 mL) dried over MgSO4 filtered concentrated under reduced pressure The resulting solid was absorbed onto Celite® gradient elution

反応条件: temp:-78.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: To a solution of (E)-ethyl 3-(4-bromophenyl)acrylate (25 g, 96 mmol) in DCM (300 ml) under nitrogen and cooled to −78° C. was added dropwise DIBAL-H (240 ml, 1M in DCM, 240 mmol) in about 20 minutes. The mixture was stirred at −78° C. for 2 hours. Then, the dry ice bath was removed. The reaction was diluted with DCM (500 mL), quenched with HCl (1N), and partitioned. The combined organic phases were washed with H2O, dried and concentrated under reduced pressure to provide the title compound. 1H NMR (300 MHz, CDCl3): 1.43 (t, J=6 Hz, 1H), 4.32 (t, J=4.5 Hz, 2H), 6.37 (dt, J=16.5 Hz, J=6 Hz, 1H), 6.57 (d, J=15 Hz, 1H), 7.25 (d, J=9 Hz, 2H), 7.45 (d, J=9 Hz, 2H). MS (DCl—NH3) m/z 214 (M+H)+. Then, the dry ice bath was removed The reaction was diluted with DCM (500 mL) quenched with HCl (1N) partitioned The combined organic phases were washed with H2O dried concentrated under reduced pressure