4-(2-oxoethyl)benzonitrile

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

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

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

Procedure: Acetic acid (11.5 mL) was added to a dichloromethane solution (450 mL) of the compound (17.7 g) obtained in Step 6 and the compound (19.4 g) obtained in Step 1 of Example 1 at room temperature and the mixture was stirred at the same temperature for thirty minutes. Sodium triacetoxyborohydride (56.6 g) was added to the mixture under cooling with ice-water and the mixture was stirred at the same temperature for thirty minutes and further stirred at room temperature for five hours. The solvent was removed under reduced pressure and insoluble matter (16.1 g) precipitated by adding water (250 mL) and ethyl acetate (250 mL) was collected by filtration. To the obtained insoluble matter (13.0 g) was added water (50 mL) and saturated aqueous sodium hydrogencarbonate solution (150 mL) and the residue was extracted with ethyl acetate. The organic layer was washed with brine and dried over anhydrous sodium sulfate, and the solvent was removed under reduced pressure. The obtained residue was crystallized from ether-hexane to obtain the titled compound (10.3 g) as crystals. The physical data of the obtained compound accord with those of the compound of Example 3. further stirred at room temperature for five hours The solvent was removed under reduced pressure and insoluble matter (16.1 g) precipitated by adding water (250 mL) and ethyl acetate (250 mL) was collected by filtration To the obtained insoluble matter (13.0 g) was added water (50 mL) and saturated aqueous sodium hydrogencarbonate solution (150 mL) the residue was extracted with ethyl acetate The organic layer was washed with brine dried over anhydrous sodium sulfate the solvent was removed under reduced pressure The obtained residue was crystallized from ether-hexane

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

Procedure: This compound was prepared from 4-cyanobenzaldehyde using a modification of a procedure previously used in the multi-step synthesis of 2-phenylpropanal {Allen, C. F. H.; van Allan, J., Org. Syn. Coll. Vol 3, 733-734 (1955)}.

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

Procedure: This compound was prepared from 4-cyanobenzaldehyde using a modification of a procedure previously used in the multi-step synthesis of 2-phenylpropanal {Allen, C. F. H.; van Allan, J., Org. Syn. Coll. Vol 3, 733-734 (1955)}.

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

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

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

Procedure: This compound was synthesized from crude 4-cyanophenylacetaldehyde, benzyl carbamate, and triphenylphosphite using a modification of the previously described amidoalkylation procedure.9Benzyl carbamate (6.1 g, 40 mmole) and 4-cyanophenylacetaldehyde (4.7 g, 32 mmole) were dissolved in 50 mL toluene and refluxed for 1 h. The toluene was evaporated, glacial acetic acid (10 mL) and triphenyl phosphite (8.5 mL, 32 mmole) were added to the residue, and the mixture was heated at 80 ° C. for 2 h. The volatile materials were removed by evaporation in vacuo and the resulting oil was dissolved in 50 mL methanol. The solution was refrigerated overnight and the white precipitate was filtered, dried, and recrystallized from 50 mL hot methanol. The undissolved product was discarded, and the filtrate was cooled down to give white crystals, yield 25-35%; mp 136°-137° C.; 1H NMR (DMSO) δ8.20 (d, 1H), 7.75 (d, 2H), 7.54 (d, 2H), 7.35 (m, 5H), 7.3-7.1 (m, 10H), 4.95 (q, 2H), 4.60 (m, 1H), 3.4-3.0 (m, 2H); MS (FAB+) m/e 513 (m+1). Anal. (C29H25N2O5P) C, H, N. refluxed for 1 h The toluene was evaporated The volatile materials were removed by evaporation in vacuo the resulting oil was dissolved in 50 mL methanol the white precipitate was filtered dried recrystallized from 50 mL hot methanol the filtrate was cooled down to give white crystals, yield 25-35%

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

Procedure: This compound was synthesized from crude 4-cyanophenylacetaldehyde, benzyl carbamate, and triphenylphosphite using a modification of the previously described amidoalkylation procedure.9Benzyl carbamate (6.1 g, 40 mmole) and 4-cyanophenylacetaldehyde (4.7 g, 32 mmole) were dissolved in 50 mL toluene and refluxed for 1 h. The toluene was evaporated, glacial acetic acid (10 mL) and triphenyl phosphite (8.5 mL, 32 mmole) were added to the residue, and the mixture was heated at 80 ° C. for 2 h. The volatile materials were removed by evaporation in vacuo and the resulting oil was dissolved in 50 mL methanol. The solution was refrigerated overnight and the white precipitate was filtered, dried, and recrystallized from 50 mL hot methanol. The undissolved product was discarded, and the filtrate was cooled down to give white crystals, yield 25-35%; mp 136°-137° C.; 1H NMR (DMSO) δ8.20 (d, 1H), 7.75 (d, 2H), 7.54 (d, 2H), 7.35 (m, 5H), 7.3-7.1 (m, 10H), 4.95 (q, 2H), 4.60 (m, 1H), 3.4-3.0 (m, 2H); MS (FAB+) m/e 513 (m+1). Anal. (C29H25N2O5P) C, H, N. refluxed for 1 h The toluene was evaporated The volatile materials were removed by evaporation in vacuo the resulting oil was dissolved in 50 mL methanol the white precipitate was filtered dried recrystallized from 50 mL hot methanol the filtrate was cooled down to give white crystals, yield 25-35%

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

Procedure: This compound was synthesized from crude 4-cyanophenylacetaldehyde, benzyl carbamate, and triphenylphosphite using a modification of the previously described amidoalkylation procedure.9Benzyl carbamate (6.1 g, 40 mmole) and 4-cyanophenylacetaldehyde (4.7 g, 32 mmole) were dissolved in 50 mL toluene and refluxed for 1 h. The toluene was evaporated, glacial acetic acid (10 mL) and triphenyl phosphite (8.5 mL, 32 mmole) were added to the residue, and the mixture was heated at 80 ° C. for 2 h. The volatile materials were removed by evaporation in vacuo and the resulting oil was dissolved in 50 mL methanol. The solution was refrigerated overnight and the white precipitate was filtered, dried, and recrystallized from 50 mL hot methanol. The undissolved product was discarded, and the filtrate was cooled down to give white crystals, yield 25-35%; mp 136°-137° C.; 1H NMR (DMSO) δ8.20 (d, 1H), 7.75 (d, 2H), 7.54 (d, 2H), 7.35 (m, 5H), 7.3-7.1 (m, 10H), 4.95 (q, 2H), 4.60 (m, 1H), 3.4-3.0 (m, 2H); MS (FAB+) m/e 513 (m+1). Anal. (C29H25N2O5P) C, H, N. refluxed for 1 h The toluene was evaporated The volatile materials were removed by evaporation in vacuo the resulting oil was dissolved in 50 mL methanol the white precipitate was filtered dried recrystallized from 50 mL hot methanol the filtrate was cooled down to give white crystals, yield 25-35%

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

Procedure: This compound was prepared from 4-cyanobenzaldehyde using a modification of a procedure previously used in the multi-step synthesis of 2-phenylpropanal [Allen, C. F. H.; van Allan, J. Org. Syn. Coll. Vol 3, 733-734 (1955)].

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

Procedure: A mixture of 5-[2-(piperazin-1-yl)ethyl]-2-benzofuran-1(3H)-one (50 mg, 0.20 mmol), 4-(2-Oxoethyl)benzonitrile (30 mg, 0.20 mmol), Sodium Cyanoborohydride (13 mg, 0.20 mmol), and a drop of HOAc was stirred together in Methanol for 2 hours. LC showed formation of the desired product. The crude was diluted with EtOAc, washed with water, adsorbed onto silica gel, and purified by silica gel chromatography. LC-MS (IE, m/z): 376 [M+1]+. (0.30 μM)