4-(piperidin-1-ylmethyl)phenol

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

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

Procedure: The title compound was prepared using methods analogous to those described for Intermediate 35, substituting DCE for CH2Cl2. 1H NMR (500 MHz, CDCl3): 7.14-7.03 (m, 2H), 6.75 (br s, 1H), 6.62-6.53 (m, 2H), 3.41 (s, 2H), 2.49 (s, 4H), 1.66-1.59 (m, 4H), 1.50-1.42 (m, 2H). MS (ESI): mass calcd. for C12H17NO, 191.13; m/z found, 192.20 [M+H]+.

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

Procedure: The title compound was prepared using methods analogous to those described for Intermediate 35, substituting DCE for CH2Cl2. 1H NMR (500 MHz, CDCl3): 7.14-7.03 (m, 2H), 6.75 (br s, 1H), 6.62-6.53 (m, 2H), 3.41 (s, 2H), 2.49 (s, 4H), 1.66-1.59 (m, 4H), 1.50-1.42 (m, 2H). MS (ESI): mass calcd. for C12H17NO, 191.13; m/z found, 192.20 [M+H]+.

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

Procedure: A suspension of the product of Example 17 (176 mg), 2-Diethylamino-ethanol (0.12 mL), and polymer supported triphenylphosphine (613 mg; loading: 3 mmol/g) in DCM (5 mL) was treated with di-tert-butylazodicarboxylate (316 mg). After 2 h, the resulting mixture was filtered, and the filtrate was evaporated. Chromatography of the residue (3% 2 M methanolic ammonia/DCM) gave the title compound as a pale yellow oil (37 mg). 1H NMR (400 MHz, CDCl3): 7.20 (d, J=8.8 Hz, 2H), 6.84 (d, J=8.6 Hz, 2H), 4.03 (t, J=6.5 Hz, 2H), 3.40 (s, 2H), 2.87 (t, J=6.5 Hz, 2H), 2.63 (q, J=7.0 Hz, 4H), 2.35 (br s, 4H), 1.59-1.52 (m, 4H), 1.46-1.37 (m, 2H), 1.07 (t, J=7.1 Hz, 6H). the resulting mixture was filtered the filtrate was evaporated

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

Procedure: A suspension of the product of Example 17 (176 mg), 3-(2-methyl-piperidin-1-yl)-propan-1-ol (145 mg), and polymer supported triphenylphosphine (613 mg; loading: 3 mmol/g) in DCM (5 mL) was treated with di-tert-butylazodicarboxylate (316 mg). After 2 h, the resulting mixture was filtered, and the filtrate was evaporated. Chromatography of the residue (2.5% 2 M methanolic ammonia/DCM) gave the title compound as a colorless oil (60 mg). 1H NMR (400 MHz, CDCl3): 7.20 (d, J=8.6 Hz, 2H), 6.83 (d, J=8.6 Hz, 2H), 4.01-3.92 (m, 2H), 3.40 (s, 2H), 2.90-2.81 (m, 2H), 2.56-2.47 (m, 1H), 2.40-2.25 (m, 5H), 2.21-2.14 (m, 1H), 1.97-1.88 (m, 2H), 1.70-1.51 (m, 8H), 1.45-1.25 (m, 4H), 1.07 (d, J=6.2 Hz, 3H). the resulting mixture was filtered the filtrate was evaporated

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

Procedure: A solution of 4-hydroxybenzaldehyde (10 g), piperidine (8.9 mL), and acetic acid (4.7 mL) in DCE (200 mL) was treated with sodium triacetoxyborohydride (24 g). After 16 h, the resulting mixture was treated with saturated aqueous sodium bicarbonate (100 mL) and extracted with DCM (5×100 mL). The combined organic phases were dried (magnesium sulfate) and evaporated. Trituration of the residue with ethyl acetate gave the title compound as a white crystalline solid (5.5 g). extracted with DCM (5×100 mL) The combined organic phases were dried (magnesium sulfate) evaporated

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

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

Procedure: A suspension of the product of Example 17 (176 mg), 2-Diethylamino-ethanol (0.12 mL), and polymer supported triphenylphosphine (613 mg; loading: 3 mmol/g) in DCM (5 mL) was treated with di-tert-butylazodicarboxylate (316 mg). After 2 h, the resulting mixture was filtered, and the filtrate was evaporated. Chromatography of the residue (3% 2 M methanolic ammonia/DCM) gave the title compound as a pale yellow oil (37 mg). 1H NMR (400 MHz, CDCl3): 7.20 (d, J=8.8 Hz, 2H), 6.84 (d, J=8.6 Hz, 2H), 4.03 (t, J=6.5 Hz, 2H), 3.40 (s, 2H), 2.87 (t, J=6.5 Hz, 2H), 2.63 (q, J=7.0 Hz, 4H), 2.35 (br s, 4H), 1.59-1.52 (m, 4H), 1.46-1.37 (m, 2H), 1.07 (t, J=7.1 Hz, 6H). the resulting mixture was filtered the filtrate was evaporated

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

Procedure: A suspension of the product of Example 17 (176 mg), 3-(2-methyl-piperidin-1-yl)-propan-1-ol (145 mg), and polymer supported triphenylphosphine (613 mg; loading: 3 mmol/g) in DCM (5 mL) was treated with di-tert-butylazodicarboxylate (316 mg). After 2 h, the resulting mixture was filtered, and the filtrate was evaporated. Chromatography of the residue (2.5% 2 M methanolic ammonia/DCM) gave the title compound as a colorless oil (60 mg). 1H NMR (400 MHz, CDCl3): 7.20 (d, J=8.6 Hz, 2H), 6.83 (d, J=8.6 Hz, 2H), 4.01-3.92 (m, 2H), 3.40 (s, 2H), 2.90-2.81 (m, 2H), 2.56-2.47 (m, 1H), 2.40-2.25 (m, 5H), 2.21-2.14 (m, 1H), 1.97-1.88 (m, 2H), 1.70-1.51 (m, 8H), 1.45-1.25 (m, 4H), 1.07 (d, J=6.2 Hz, 3H). the resulting mixture was filtered the filtrate was evaporated

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

Procedure: A solution of 4-hydroxybenzaldehyde (10 g), piperidine (8.9 mL), and acetic acid (4.7 mL) in DCE (200 mL) was treated with sodium triacetoxyborohydride (24 g). After 16 h, the resulting mixture was treated with saturated aqueous sodium bicarbonate (100 mL) and extracted with DCM (5×100 mL). The combined organic phases were dried (magnesium sulfate) and evaporated. Trituration of the residue with ethyl acetate gave the title compound as a white crystalline solid (5.5 g). extracted with DCM (5×100 mL) The combined organic phases were dried (magnesium sulfate) evaporated

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

Procedure: The title compound was prepared using methods analogous to those described for Intermediate 35, substituting DCE for CH2Cl2. 1H NMR (500 MHz, CDCl3): 7.14-7.03 (m, 2H), 6.75 (br s, 1H), 6.62-6.53 (m, 2H), 3.41 (s, 2H), 2.49 (s, 4H), 1.66-1.59 (m, 4H), 1.50-1.42 (m, 2H). MS (ESI): mass calcd. for C12H17NO, 191.13; m/z found, 192.20 [M+H]+.

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

Procedure: A solution of 4-hydroxybenzaldehyde (10 g), piperidine (8.9 mL), and acetic acid (4.7 mL) in DCE (200 mL) was treated with sodium triacetoxyborohydride (24 g). After 16 h, the resulting mixture was treated with saturated aqueous sodium bicarbonate (100 mL) and extracted with DCM (5×100 mL). The combined organic phases were dried (magnesium sulfate) and evaporated. Trituration of the residue with ethyl acetate gave the title compound as a white crystalline solid (5.5 g). extracted with DCM (5×100 mL) The combined organic phases were dried (magnesium sulfate) evaporated