4-氨基-3-氯-5-三氟甲基苯甲醛

反应条件: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

实验步骤: Analogously to the sequence described in 9f to 9i, 1-methyl (S)-2-(4-amino-3-chloro-5-trifluoromethyl-benzyl)-succinate and (S)-2-(4-amino-3-chloro-5-trifluoromethyl-benzyl)-4-oxo-4-[4-(2-oxo-1,2,4,5-tetrahydro-1,3-benzodiazepin-3-yl)-piperidin-1-yl]-butanoic acid were able to be obtained from 4-amino-3-chloro-5-trifluoromethyl-benzaldehyde (see Example 1b).

反应条件: temp:35.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

实验步骤: Under a nitrogen atmosphere 3.93 g (90.0 mmol) of NaH (55% in mineral oil) were added batchwise to a solution of 31.98 g (90.0 mmol) of diethyl[2-((R)-4-benzyl-2-oxo-oxazolidin-3-yl)-2-oxo-ethyl]-phosphonate in 400 mL of THF. The reaction mixture was stirred for 30 min at RT and for a further 35 min at 35° C. After the development of gas had ended, 16.0 g (71.5 mmol) of 4-amino-3-chloro-5-trifluoromethyl-benzaldehyde, dissolved in 50 mL THF, were added dropwise and stirred for a further 12 h at RT. The reaction solution was combined with saturated NH4Cl solution, the mixture was extracted exhaustively with EtOAc and the combined extracts were dried and evaporated down i. vac. The residue remaining was purified by chromatography on silica gel. The desired product was obtained in the form of a yellow oil. were added dropwise stirred for a further 12 h at RT the mixture was extracted exhaustively with EtOAc the combined extracts were dried evaporated down i The residue remaining was purified by chromatography on silica gel

反应条件: temp:35.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

实验步骤: Under a nitrogen atmosphere 3.93 g (90.0 mmol) of NaH (55% in mineral oil) were added batchwise to a solution of 31.98 g (90.0 mmol) of diethyl[2-((R)-4-benzyl-2-oxo-oxazolidin-3-yl)-2-oxo-ethyl]-phosphonate in 400 mL of THF. The reaction mixture was stirred for 30 min at RT and for a further 35 min at 35° C. After the development of gas had ended, 16.0 g (71.5 mmol) of 4-amino-3-chloro-5-trifluoromethyl-benzaldehyde, dissolved in 50 mL THF, were added dropwise and stirred for a further 12 h at RT. The reaction solution was combined with saturated NH4Cl solution, the mixture was extracted exhaustively with EtOAc and the combined extracts were dried and evaporated down i. vac. The residue remaining was purified by chromatography on silica gel. The desired product was obtained in the form of a yellow oil. were added dropwise stirred for a further 12 h at RT the mixture was extracted exhaustively with EtOAc the combined extracts were dried evaporated down i The residue remaining was purified by chromatography on silica gel

反应条件: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

实验步骤: A mixture of 17.0 g (75.4 mmol) of (4-amino-3-chloro-5-trifluoromethyl-phenyl)-methanol, 100 g (1.15 mol) of manganese dioxide and 300 mL of DCM was stirred overnight at RT. The precipitate was suction filtered and the solution evaporated down i. vac. The desired product was obtained as a white solid. filtered the solution evaporated down i

反应条件: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

实验步骤: A mixture of 17.0 g (75.4 mmol) of (4-amino-3-chloro-5-trifluoromethyl-phenyl)-methanol, 100 g (1.15 mol) of manganese dioxide and 300 mL of DCM was stirred overnight at RT. The precipitate was suction filtered and the solution evaporated down i. vac. The desired product was obtained as a white solid. filtered the solution evaporated down i

反应条件: temp:128.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

实验步骤: A mixture of 50.0 g (224 mmol) 4-amino-3-chloro-5-trifluoromethyl-benzaldehyde, 39.3 g (335 mmol) N-acetylglycine, 27.5 g (335 mmol) sodium acetate and 200 ml acetic anhydride was stirred for 2 hours in an oil bath at an oil bath temperature of 128° C. After cooling to an oil bath temperature of 90° C. 100 ml of water were added dropwise and the resulting suspension was added to a mixture of 1000 ml of water and 500 ml of toluene. The precipitate formed was suction filtered, washed with 300 ml of toluene and 500 ml of water and dried overnight at 60° C. in the circulating air dryer. After cooling to an oil bath temperature of 90° C The precipitate formed filtered washed with 300 ml of toluene and 500 ml of water dried overnight at 60° C. in the circulating air dryer

反应条件: temp:20.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

实验步骤: 26.14 kg (55.91 mol) potassium tert.butoxide solution in THF were metered into a mixture of 10.00 kg (44.73 mol) 4-amino-3-chloro-5-trifluoromethylbenzaldehyde (A), 9.31 kg (89.45 mol) methyl methoxyacetate (B) and 30.0 L tetrahydrofuran and the mixture was stirred for 24 hours at 20° C. Then 7.16 kg (89.45 mol) sodium hydroxide solution (50%) were metered in and the mixture was heated to 30° C. for 1 hour, before 16.31 kg (134.18 mol) hydrochloric acid (30%) and 15.0 L water were added. After the aqueous phase has been separated off, 40 L of the solvent were distilled off and the residue was combined with 25.0 L toluene, before another 40 L solvent were distilled off. The organic phase was combined with 20.0 L water and cooled to 23° C. After the addition of 10.0 L toluene the suspension was stirred for a further 30 minutes, the product was separated off and dried. were added After the aqueous phase has been separated off 40 L of the solvent were distilled off were distilled off cooled to 23° C After the addition of 10.0 L toluene the suspension was stirred for a further 30 minutes the product was separated off dried

反应条件: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

实验步骤: Analogously to the sequence described in 9f to 9i, 1-methyl (S)-2-(4-amino-3-chloro-5-trifluoromethyl-benzyl)-succinate and (S)-2-(4-amino-3-chloro-5-trifluoromethyl-benzyl)-4-oxo-4-[4-(2-oxo-1,2,4,5-tetrahydro-1,3-benzodiazepin-3-yl)-piperidin-1-yl]-butanoic acid were able to be obtained from 4-amino-3-chloro-5-trifluoromethyl-benzaldehyde (see Example 1b).

反应条件: temp:35.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

实验步骤: Under a nitrogen atmosphere 3.93 g (90.0 mmol) of NaH (55% in mineral oil) were added batchwise to a solution of 31.98 g (90.0 mmol) of diethyl[2-((R)-4-benzyl-2-oxo-oxazolidin-3-yl)-2-oxo-ethyl]-phosphonate in 400 mL of THF. The reaction mixture was stirred for 30 min at RT and for a further 35 min at 35° C. After the development of gas had ended, 16.0 g (71.5 mmol) of 4-amino-3-chloro-5-trifluoromethyl-benzaldehyde, dissolved in 50 mL THF, were added dropwise and stirred for a further 12 h at RT. The reaction solution was combined with saturated NH4Cl solution, the mixture was extracted exhaustively with EtOAc and the combined extracts were dried and evaporated down i. vac. The residue remaining was purified by chromatography on silica gel. The desired product was obtained in the form of a yellow oil. were added dropwise stirred for a further 12 h at RT the mixture was extracted exhaustively with EtOAc the combined extracts were dried evaporated down i The residue remaining was purified by chromatography on silica gel

反应条件: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

实验步骤: A mixture of 17.0 g (75.4 mmol) of (4-amino-3-chloro-5-trifluoromethyl-phenyl)-methanol, 100 g (1.15 mol) of manganese dioxide and 300 mL of DCM was stirred overnight at RT. The precipitate was suction filtered and the solution evaporated down i. vac. The desired product was obtained as a white solid. filtered the solution evaporated down i