1-(cyclopropylmethyl)piperidin-4-ol

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: To a cold (0° C.) solution of 1-cyclopropylmethyl-piperidin-4-one (314 mg, 2 mmol, 1.0 eq.) in ethanol (4 mL) was added sodium borohydride (61 mg, 2 mmol, 0.75 eq.). The reaction mixture was stirred 16 h at room temperature. Water, sodium hydroxide and dichloromethane were added and the reaction mixture was stirred 2 h at room temperature. The aqueous layer was extracted with dichloromethane and the combined organic phases were dried over sodium sulfate, filtered then concentrated to dryness in vacuo to yield 160 mg (50%) of the tide compound as colorless oil, witch was used in the next step without further purification. MS (m/e): 156.3 (MH+, 100%). the reaction mixture was stirred 2 h at room temperature The aqueous layer was extracted with dichloromethane the combined organic phases were dried over sodium sulfate filtered then concentrated to dryness in vacuo

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: Add NaH (60% dispersion in oil, 130 mg, 3.25 mmol) to a solution of 1-cyclopropylmethyl-piperidin-4-ol (preparation 11, 458 mg, 2.95 mmol) in DMF (8 mL) and stir for 20 min. Then add 2,6-dichloropyridine to the mixture and heat at 120° C. overnight. Quench the reaction with saturated NaHCO3, extract with methylene dichloride three times. Combine the organic layers, wash with saturated NaCl solution, dry over Na2SO4, filter and concentrate to give a residue. Chromatography (silica gel) eluting with 4% 2M NH3-methanol in methylene dichloride provides 480 mg (61%) of the title compound: mass spectrum (ion spray): m/z=267.2 (M+1); 1H NMR (CDCl3, ppm): 7.39 (t, 1H), 6.75 (d, 1H), 6.52 (d, 1H), 4.96 (m, 1H), 2.75 (m, 2H), 2.30 (m, 2H), 2.19 (d, 2H), 1.97 (m, 2H), 1.75 (m, 2H), 0.76 (m, 1H), 0.43 (m, 2H), 0.00 (m, 2H). Quench the reaction with saturated NaHCO3 extract with methylene dichloride three times Combine the organic layers, wash with saturated NaCl solution dry over Na2SO4 filter concentrate to give a residue Chromatography (silica gel) eluting with 4% 2M NH3-methanol in methylene dichloride

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

Procedure: Add bromomethylcyclopropane (2.025 g, 15 mmol) to a solution of 4-hydroxypiperidine (3.035 g, 30 mmol) in THF (10 mL) and stir the mixture overnight. Dilute the mixture with ethylacetate, wash with saturated NaHCO3 solution, dry over Na2SO4, filter and concentrate to give a residue. Chromatography (silica gel, eluting with 8% 2M NH3-methanol in CH2Cl2) provides 1.087 g (47%) of the title compound: mass spectrum (ion spray): m/z=156.2 (M+1); 1H NMR (CDCl3, ppm): 3.60 (m, 1H), 2.81 (m, 2H), 2.16 (d, 1H), 2.10 (m, 3H), 1.84 (m, 2H), 1.53 (m, 3H), 0.79 (m, 1H), 0.44 (m, 2H), 0.00 (m, 2H). wash with saturated NaHCO3 solution dry over Na2SO4 filter concentrate to give a residue Chromatography (silica gel, eluting with 8% 2M NH3-methanol in CH2Cl2)

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

Procedure: To a cold (0° C.) solution of 1-cyclopropylmethyl-piperidin-4-one (314 mg, 2 mmol, 1.0 eq.) in ethanol (4 mL) was added sodium borohydride (61 mg, 2 mmol, 0.75 eq.). The reaction mixture was stirred 16 h at room temperature. Water, sodium hydroxide and dichloromethane were added and the reaction mixture was stirred 2 h at room temperature. The aqueous layer was extracted with dichloromethane and the combined organic phases were dried over sodium sulfate, filtered then concentrated to dryness in vacuo to yield 160 mg (50%) of the tide compound as colorless oil, witch was used in the next step without further purification. MS (m/e): 156.3 (MH+, 100%). the reaction mixture was stirred 2 h at room temperature The aqueous layer was extracted with dichloromethane the combined organic phases were dried over sodium sulfate filtered then concentrated to dryness in vacuo