2-(3-piperidin-1-ylpropoxy)benzaldehyde

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

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: A solution of 2-(3-piperidin-1-yl-propoxy)-benzaldehyde (212 mg), 4-benzylidene-piperidine (154 mg), and acetic acid (0.05 mL) in DCM (3 mL) was treated with sodium triacetoxyborohydride (290 mg). After 16 h, the resulting mixture was treated with 10% sodium hydroxide (6 mL) and extracted with DCM (3×10 mL). The combined organic phases were dried (sodium sulfate) and evaporated. Chromatography of the residue (1–5% 2 M methanolic ammonia/DCM) gave the title compound as a colorless oil (148 mg). 1H NMR (400 MHz, CDCl3): 7.37 (m, 1H), 7.30 (m, 2H), 7.23–7.16 (m, 4H), 6.92 (m, 1H), 6.86 (m, 1H), 6.27 (s, 1H), 4.00 (t, J=6.3 Hz, 2H), 3.60 (s, 2H), 2.60 (m, 2H), 2.55–2.46 (m, 6H), 2.44–2.37 (m, 6H), 2.00 (m, 2H), 1.64–1.56 (m, 4H), 1.47–1.40 (m, 2H). extracted with DCM (3×10 mL) The combined organic phases were dried (sodium sulfate) evaporated

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

Procedure: A solution of 2-(3-piperidin-1-yl-propoxy)-benzaldehyde (212 mg), 4-benzylidene-piperidine (154 mg), and acetic acid (0.05 mL) in DCM (3 mL) was treated with sodium triacetoxyborohydride (290 mg). After 16 h, the resulting mixture was treated with 10% sodium hydroxide (6 mL) and extracted with DCM (3×10 mL). The combined organic phases were dried (sodium sulfate) and evaporated. Chromatography of the residue (1–5% 2 M methanolic ammonia/DCM) gave the title compound as a colorless oil (148 mg). 1H NMR (400 MHz, CDCl3): 7.37 (m, 1H), 7.30 (m, 2H), 7.23–7.16 (m, 4H), 6.92 (m, 1H), 6.86 (m, 1H), 6.27 (s, 1H), 4.00 (t, J=6.3 Hz, 2H), 3.60 (s, 2H), 2.60 (m, 2H), 2.55–2.46 (m, 6H), 2.44–2.37 (m, 6H), 2.00 (m, 2H), 1.64–1.56 (m, 4H), 1.47–1.40 (m, 2H). extracted with DCM (3×10 mL) The combined organic phases were dried (sodium sulfate) evaporated

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

Procedure: A solution of 2-(3-piperidin-1-yl-propoxy)-benzaldehyde (266 mg), 4-chloroaniline (146 mg), and acetic acid (0.07 mL) in DCM (5 mL) was treated with sodium triacetoxyborohydride (400 mg). After 16 h, the resulting mixture was treated with 10% sodium hydroxide (6 mL) and extracted with DCM (3×10 mL). The combined organic phases were dried (sodium sulfate) and evaporated. Chromatography of the residue (1–5% 2 M methanolic ammonia/DCM) gave the title compound as a colorless oil (246 mg). 1H NMR (400 MHz, CDCl3): 7.28–7.20 (m, 2H), 7.09 (d, J=8.9 Hz, 2H), 6.89 (m, 2H), 6.55 (d, J=8.9 Hz, 2H), 4.30 (d, J=5.6, 2H), 4.18 (m, 1H), 4.05 (t, J=6.3 Hz, 2H), 2.47 (m, 2H), 2.37 (br, 4H), 1.96 (m, 2H), 1.62–1.56 (m, 4H), 1.49–1.42 (m, 2H). extracted with DCM (3×10 mL) The combined organic phases were dried (sodium sulfate) evaporated

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

Procedure: A solution of 2-(3-piperidin-1-yl-propoxy)-benzaldehyde (269 mg), 2-aminopyridine (110 mg), and acetic acid (0.07 mL) in DCM (5 mL) was treated with sodium triacetoxyborohydride (410 mg). After 16 h, the resulting mixture was treated with 10% sodium hydroxide (6 mL) and extracted with DCM (3×10 mL). The combined organic phases were dried (sodium sulfate) and evaporated. Chromatography of the residue (1–5% 2 M methanolic ammonia/DCM) gave the title compound as a colorless oil (128 mg). 1H NMR (400 MHz, CDCl3): 8.07 (m, 1H), 7.37 (m, 1H), 7.29 (m, 1H), 7.22 (m, 1H), 6.91–6.84 (m, 2H), 6.54 (m, 1H), 6.37 (m, 1H), 5.00 (m, 1H), 4.48 (d, J=5.6, 2H), 4.04 (t, J=6.3 Hz, 2H), 2.52 (m, 2H), 2.41 (br, 4H), 2.02 (m, 2H), 1.64–1.57 (m, 4H), 1.47–1.40 (m, 2H). extracted with DCM (3×10 mL) The combined organic phases were dried (sodium sulfate) evaporated

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

Procedure: A solution of 2-(3-piperidin-1-yl-propoxy)-benzaldehyde (212 mg), 4-benzylidene-piperidine (154 mg), and acetic acid (0.05 mL) in DCM (3 mL) was treated with sodium triacetoxyborohydride (290 mg). After 16 h, the resulting mixture was treated with 10% sodium hydroxide (6 mL) and extracted with DCM (3×10 mL). The combined organic phases were dried (sodium sulfate) and evaporated. Chromatography of the residue (1-5% 2 M methanolic ammonia/DCM) gave the title compound as a colorless oil (148 mg). 1H NMR (400 MHz, CDCl3): 7.37 (m, 1H), 7.30 (m, 2H), 7.23-7.16 (m, 4H), 6.92 (m, 1H), 6.86 (m, 1H), 6.27 (s, 1H), 4.00 (t, J=6.3 Hz, 2H), 3.60 (s, 2H), 2.60 (m, 2H), 2.55-2.46 (m, 6H), 2.44-2.37 (m, 6H), 2.00 (m, 2H), 1.64-1.56 (m, 4H), 1.47-1.40 (m, 2H). extracted with DCM (3×10 mL) The combined organic phases were dried (sodium sulfate) evaporated

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

Procedure: A solution of 2-(3-piperidin-1-yl-propoxy)-benzaldehyde (266 mg), 4-chloroaniline (146 mg), and acetic acid (0.07 mL) in DCM (5 mL) was treated with sodium triacetoxyborohydride (400 mg). After 16 h, the resulting mixture was treated with 10% sodium hydroxide (6 mL) and extracted with DCM (3×10 mL). The combined organic phases were dried (sodium sulfate) and evaporated. Chromatography of the residue (1-5% 2 M methanolic ammonia/DCM) gave the title compound as a colorless oil (246 mg). 1H NMR (400 MHz, CDCl3): 7.28-7.20 (m, 2H), 7.09 (d, J=8.9 Hz, 2H), 6.89 (m, 2H), 6.55 (d, J=8.9 Hz, 2H), 4.30 (d, J=5.6, 2H), 4.18 (m, 1H), 4.05 (t, J=6.3 Hz, 2H), 2.47 (m, 2H), 2.37 (br, 4H), 1.96 (m, 2H), 1.62-1.56 (m, 4H), 1.49-1.42 (m, 2H). extracted with DCM (3×10 mL) The combined organic phases were dried (sodium sulfate) evaporated

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

Procedure: A solution of 2-(3-piperidin-1-yl-propoxy)-benzaldehyde (269 mg), 2-aminopyridine (110 mg), and acetic acid (0.07 mL) in DCM (5 mL) was treated with sodium triacetoxyborohydride (410 mg). After 16 h, the resulting mixture was treated with 10% sodium hydroxide (6 mL) and extracted with DCM (3×10 mL). The combined organic phases were dried (sodium sulfate) and evaporated. Chromatography of the residue (1-5% 2 M methanolic ammonia/DCM) gave the title compound as a colorless oil (128 mg). 1H NMR (400 MHz, CDCl3): 8.07 (m, 1H), 7.37 (m, 1H), 7.29 (m, 1H), 7.22 (m, 1H), 6.91-6.84 (m, 2H), 6.54 (m, 1H), 6.37 (m, 1H), 5.00 (m, 1H), 4.48 (d, J=5.6, 2H), 4.04 (t, J=6.3 Hz, 2H), 2.52 (m, 2H), 2.41 (br, 4H), 2.02.(m, 2H), 1.64-1.57 (m, 4H), 1.47-1.40 (m, 2H). extracted with DCM (3×10 mL) The combined organic phases were dried (sodium sulfate) evaporated

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

Procedure: 2-[3-(1-Piperidinyl)propoxy]benzaldehyde (47.6 g) is reacted with 24 g of phenethylamine in 190 ml of toluene following the procedure described in Example 1A to yield 61.9 g of product as an oil, boiling point 214°-218° C. at 0.2-0.3 mm of Hg.

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

Procedure: Salicylaldehyde (27 g) is treated first with 11 g of 50% sodium hydride in 175 ml of dimethylformamide and then with 150 ml of a 2 N toluene solution of N-(3-chloropropyl)-piperidine following the procedure described in Example 31A, yielding 47.7 g of the title compound as an oil, boiling point 155°-160° C. at 0.2-0.3 mm of Hg.