2,5-dichlorobenzaldehyde

Conditions: temp:0.00; pressure:0.00; stir:

Conditions: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: To a solution of 2,5-dichlorbenzaldehyde (4.0 g, 0.0228 mole) in ethanol (6 ml) was added malononitrile (1.52 g, 0.0228 mole), followed by 100 μl, of 10% KOH/H2O. The mixture was stirred at room temperature for 2 hrs and then filtered to give 2-(2,5-Dichloro-benzylidene)-malononitrile (8a, 4.82 g) in 95% yield. 1H-NMR (400 MHz, d6-DMSO): δ ppm 8.66 (s, 1H), 8.07 (d, J=2.0 Hz, 1H), 7.74 (s, 1H), 7.74 (s, 1H). MS [m+H] calc'd for C10H4Cl2N2, 223.0, 224.8; found 223.0, 224.8. filtered

Conditions: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: To a solution of 2,5-dichlorbenzaldehyde (4.0 g, 0.0228 mole) in ethanol (6 ml) was added malononitrile (1.52 g, 0.0228 mole), followed by 100 μl, of 10% KOH/H2O. The mixture was stirred at room temperature for 2 hrs and then filtered to give 2-(2,5-Dichloro-benzylidene)-malononitrile (8a, 4.82 g) in 95% yield. 1H-NMR (400 MHz, d6-DMSO): δ ppm 8.66 (s, 1H), 8.07 (d, J=2.0 Hz, 1H), 7.74 (s, 1H), 7.74 (s, 1H). MS [m+H] calc'd for C10H4Cl2N2, 223.0, 224.8; found 223.0, 224.8. filtered

Conditions: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: The title compound was prepared from 2,5-dichlorobenzaldehyde, 3-aminopyrazole and ethyl 3-ketohexanoate in the same manner as in Example 25.

Conditions: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: The synthesis was carried out according to the procedure of Example 1, except that 5.0 g (0.028 mole) of 2,5-dichlorobenzaldehyde were used instead of 3-methoxybenzaldehyde. The reaction steps involving Grignard reaction, oxidation and Mannich reaction led to a total yield of 1.4 g (14%) of (2RS)-2-benzyl-1-(2,4-dichlorophenyl)-3-dimethylaminopropan-1-one hydrochloride with a melting point of 140° C. The reaction steps Grignard reaction, oxidation and Mannich reaction

Conditions: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: The synthesis was carried out according to the procedure of Example 1, except that 5.0 g (0.028 mole) of 2,5-dichlorobenzaldehyde were used instead of 3-methoxybenzaldehyde. The reaction steps involving Grignard reaction, oxidation and Mannich reaction led to a total yield of 1.4 g (14%) of (2RS)-2-benzyl-1-(2,4-dichlorophenyl)-3-dimethylaminopropan-1-one hydrochloride with a melting point of 140° C. The reaction steps Grignard reaction, oxidation and Mannich reaction

Conditions: temp:0.00; pressure:0.00; stir:

Conditions: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: prepared by reaction of cyclopropylamine with 2,5-dichloro-benzaldehyde.

Conditions: temp:80.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: To a stirred solution of 4-aminobenzoic acid methyl ester (1.5 g, 10 mmol) and 2,5-dichloro-benzaldehyde (1.8 g, 10 mmol) in MeCN (5 mL) were added isobutene (2.1 mL, 30 mmol) and ytterbium(III) trifluoromethanesulfonate (Yb(OTf)3) (1.3 g, 2 mmol). The resulting mixture was stirred at 80° C. for 18 hours in sealed tube. The mixture was diluted with water (50 mL), extracted with diethyl ether (50 mL×3). The extracts were washed with water (100 mL) and brine (100 mL) and then dried over anhydrous Na2SO4. The solvent was removed in vacuo and the residue was purified by ISCO combi-flash chromatography (gradient elution, 0-10% ethyl acetate in petroleum ether) to 2-(2,5-dichloro-phenyl)-4,4-dimethyl-1,2,3,4-tetrahydro-quinoline-6-carboxylic acid methyl ester (1.8 g, 50%) as a light yellow solid (reference: Kiselyov, A. S. et al., Tetrahedron 54 (1998) 5089): MS (ESI+) [(M+H)+] 364.2. extracted with diethyl ether (50 mL×3) The extracts were washed with water (100 mL) and brine (100 mL) dried over anhydrous Na2SO4 The solvent was removed in vacuo the residue was purified by ISCO combi-flash chromatography (gradient elution, 0-10% ethyl acetate in petroleum ether) to 2-(2,5-dichloro-phenyl)-4,4-dimethyl-1,2,3,4-tetrahydro-quinoline-6-carboxylic acid methyl ester (1.8 g, 50%) as a light yellow solid (reference

Conditions: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: In a manner similar to the method described in Example 227b, 2,5-dichloro-benzaldehyde (5 g, 28.57 mmol) was reacted with 6-chlorooxindole (4.77 g, 28.57 mmol) and pyrrolidine (2.43 g, 34.3 mmol) in methanol to give title compound as yellow solid (10 g).

Conditions: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: In water (500 ml) was dissolved sodium hydroxide (4.0 g), and to the mixture was added acetone (100 ml), and then 2,5-dichlorobenzaldehyde (15.9 g). The mixture was stirred at room temperature for 1 hour, and acetone was evaporated under reduced pressure. The residue was extracted with ethyl acetate, and the organic layer was washed with water and saturated brine, and concentrated under reduced pressure to give 4-(2,5-dichlorophenyl)-3-buten-2-one (19.0 g). acetone was evaporated under reduced pressure The residue was extracted with ethyl acetate the organic layer was washed with water and saturated brine concentrated under reduced pressure

Conditions: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: In analogy to example 170, step 1, 5-acetyl-2-methoxypyridine was reacted with 2,5-dichlorobenzaldehyde in the presence of potassium hydroxide to give the title compound as a colourless solid. MS (ESI+): m/z=308.1 [M+H]+.