2-(4-hydroxypiperidin-1-yl)acetonitrile

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: The method follows that of S6 using 4-hydroxy-piperidin-1-yl-acetonitrile (18.97 g, 0.136 mol), LiAlH4 (15.48 g, 0.408 mol) and dry THF (150 mL). The title compound (8.56 g, 44%) was afforded as a straw-coloured oil after kugelrohr distillation (178° C., 0.05 mbar). δH(250 MHz; CDCl3); 1.55 (m, 2H, 1×CHCH2CH2 and 1×CH2CH2CH), 1.85 (m, 2H, 1×CHCH2CH2 and 1×CH2CH2CH), 2-2.25 (m, 5H, NCH2CH2, NCH2CH2 and OH), 2.38 (t, 2H, H2NCH2CH2N), 2.72 (t, 4H, H2NCH2CH2N, NH2) and 3.65 (m, 1H, CH2CHOH); δC(62.9 MHz; CDCl3); 34.56, 38.98, 51.35, 60.84 and 67.64; FAB MS, m/z(M+H)+ 145; IR υmax/cm−1; 3375 (broad), 1600, 1460, 1370, 1290 and 1070.

Conditions: temp:47.51; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: BrCH2CN (28.55 g, 0.238 mmol) was added dropwise to a solution of 4-hydroxypiperidine (24.98 g, 0.216 mol) and Et3N (33.18 mL, 0.238 mmol) in dry THF (100 mL) under N2, maintaining the temperature between 45-50° C. After addition of BrCH2CN, the solution was refluxed for 30 min., before allowing the solution to cool down to room temperature. The title-compound was afforded as a straw-coloured oil (18.97 g, 63%) after purification by flash chromatography using ether/CH3OH (19:1) as eluent. dH (250 MHz; CDCl3); 1.65 (m, 2H, 1×CH2CH2CH and 1×CHCH2CH2), 1.75 (s, 1H, OH), 1.95 (m, 2H, 1×CH2CH2CH, 1×CHCH2CH2), 2.45 (m, 2H, 1×NCH2CH2 and 1×NCH2CH2), 2.78 (m, 2H, 1×NCH2CH2 and 1×NCH2CH2), 3.55 (s, 2H, NCH2CN) and 3.75 (m, 1H, CH2CHOH); δC (62.9 MHz; CDCl3); 33.96, 46.09, 49.73, 66.58 and 114.71 (CN); IR υmax/cm−1; 3375(broad), 2230, 1420, 1330, 1150 and 1060; FAB MS, m/z(M+H)+ 141. the solution was refluxed for 30 min. to cool down to room temperature

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

Procedure: The method follows that of S6 using 4-hydroxy-piperidin-1-yl-acetonitrile (18.97 g, 0.136 mol), LiAlH4 (15.48 g, 0.408 mol) and dry THF (150 mL). The title compound (8.56 g, 44%) was afforded as a straw-coloured oil after kugelrohr distillation (178° C., 0.05 mbar). δH(250 MHz; CDCl3); 1.55 (m, 2H, 1×CHCH2CH2 and 1×CH2CH2CH), 1.85 (m, 2H, 1×CHCH2CH2 and 1×CH2CH2CH), 2-2.25 (m, 5H, NCH2CH2, NCH2CH2 and OH), 2.38 (t, 2H, H2NCH2CH2N), 2.72 (t, 4H, H2NCH2CH2N, NH2) and 3.65 (m, 1H, CH2CHOH); δC(62.9 MHz; CDCl3); 34.56, 38.98, 51.35, 60.84 and 67.64; FAB MS, m/z(M+H)+ 145; IR υmax/cm−1; 3375 (broad), 1600, 1460, 1370, 1290 and 1070.

Conditions: temp:47.51; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: BrCH2CN (28.55 g, 0.238 mmol) was added dropwise to a solution of 4-hydroxypiperidine (24.98 g, 0.216 mol) and Et3N (33.18 mL, 0.238 mmol) in dry THF (100 mL) under N2, maintaining the temperature between 45-50° C. After addition of BrCH2CN, the solution was refluxed for 30 min., before allowing the solution to cool down to room temperature. The title-compound was afforded as a straw-coloured oil (18.97 g, 63%) after purification by flash chromatography using ether/CH3OH (19:1) as eluent. dH (250 MHz; CDCl3); 1.65 (m, 2H, 1×CH2CH2CH and 1×CHCH2CH2), 1.75 (s, 1H, OH), 1.95 (m, 2H, 1×CH2CH2CH, 1×CHCH2CH2), 2.45 (m, 2H, 1×NCH2CH2 and 1×NCH2CH2), 2.78 (m, 2H, 1×NCH2CH2 and 1×NCH2CH2), 3.55 (s, 2H, NCH2CN) and 3.75 (m, 1H, CH2CHOH); δC (62.9 MHz; CDCl3); 33.96, 46.09, 49.73, 66.58 and 114.71 (CN); IR υmax/cm−1; 3375(broad), 2230, 1420, 1330, 1150 and 1060; FAB MS, m/z(M+H)+ 141. the solution was refluxed for 30 min. to cool down to room temperature

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: DAST (4.36 mL, 33 mmol) was added to a solution of (4-hydroxy-piperidin-1-yl)-acetonitrile (4.25 g, 30 mmol) in DCM (80 mL) at −30° C., the mixture was then stirred at rt for overnight. The reaction was cooled to −30° C. and quenched with methanol (10 mL) for 30 mins. The organic layer was then washed with NaHCO3 and dried. The residue was purified on a silica gel column to give 3 g (71%) of (4-fluoro-piperidin-1-yl)-acetonitrile. The reaction was cooled to −30° C. quenched with methanol (10 mL) for 30 mins The organic layer was then washed with NaHCO3 dried The residue was purified on a silica gel column

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

Procedure: A mixture of 4-hydroxypyridine (4.04 g, 40 mmol), chloroacetonitrile (2.78 mL, 44 mmol) and potassium carbonate (22 g, 160 mmol) in acetonitrile (50 mL) was stirred at rt for overnight. The insolubles were filtered off, the filtrate was concentrated to give 5.6 g of (4-hydroxy-piperidin-1-yl)-acetonitrile. The insolubles were filtered off the filtrate was concentrated

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

Procedure: The method follows that of S6 using 4-hydroxy-piperidin-1-yl-acetonitrile (18.97 g, 0.136 mol), LiAlH4 (15.48 g, 0.408 mol) and dry THF (150 mL). The title compound (8.56 g, 44%) was afforded as a straw-coloured oil after kugelrohr distillation (178° C., 0.05 mbar). δH(250 MHz; CDCl3); 1.55 (m, 2H, 1×CHCH2CH2 and 1×CH2CH2CH), 1.85 (m, 2H, 1×CHCH2CH2 and 1×CH2CH2CH), 2-2.25 (m, 5H, NCH2CH2, NCH2CH2 and OH), 2.38 (t, 2H, H2NCH2CH2N), 2.72 (t, 4H, H2NCH2CH2N, NH2) and 3.65 (m, 1H, CH2CHOH); δC(62.9 MHz; CDCl3); 34.56, 38.98, 51.35, 60.84 and 67.64; FAB MS, m/z(M+H)+ 145; IR υmax/cm−1; 3375 (broad), 1600, 1460, 1370, 1290 and 1070.

Conditions: temp:47.51; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: BrCH2CN (28.55 g, 0.238 mmol) was added dropwise to a solution of 4-hydroxypiperidine (24.98 g, 0.216 mol) and Et3N (33.18 mL, 0.238 mmol) in dry THF (100 mL) under N2, maintaining the temperature between 45-50° C. After addition of BrCH2CN, the solution was refluxed for 30 min., before allowing the solution to cool down to room temperature. The title-compound was afforded as a straw-coloured oil (18.97 g, 63%) after purification by flash chromatography using ether/CH3OH (19:1) as eluent. dH (250 MHz; CDCl3); 1.65 (m, 2H, 1×CH2CH2CH and 1×CHCH2CH2), 1.75 (s, 1H, OH), 1.95 (m, 2H, 1×CH2CH2CH, 1×CHCH2CH2), 2.45 (m, 2H, 1×NCH2CH2 and 1×NCH2CH2), 2.78 (m, 2H, 1×NCH2CH2 and 1×NCH2CH2), 3.55 (s, 2H, NCH2CN) and 3.75 (m, 1H, CH2CHOH); δC (62.9 MHz; CDCl3); 33.96, 46.09, 49.73, 66.58 and 114.71 (CN); IR υmax/cm−1; 3375(broad), 2230, 1420, 1330, 1150 and 1060; FAB MS, m/z(M+H)+ 141. the solution was refluxed for 30 min. to cool down to room temperature