ethyl 2-piperidin-2-ylacetate

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

Procedure: A stirred solution of ethyl piperidin-2-ylacetate (8.0 g, 0.047 mole) and ethyl 4-bromobutyrate (6.7 ml, 0.047 mole) in acetone (100 ml) was treated with potassium carbonate (13 g, 0.094 mole) and heated under reflux for 32 h. A further 1.5 ml of ethyl 4-bromobutyrate and 3 g of potassium carbonate was added and reflux continued for 16 h. The mixture was concentrated in vacuo and the residue treated with water (100 ml) and extracted with ethyl acetate (2×100 ml). The combined extracts were dried (Na2SO4), concentrated in vacuo and the residue chromatographed on silica gel eluting with ether/petrol (60-80) to afford the title compound as a pale yellow oil (11.5 g, 86%) heated under reflux for 32 h reflux The mixture was concentrated in vacuo the residue treated with water (100 ml) extracted with ethyl acetate (2×100 ml) The combined extracts were dried (Na2SO4) concentrated in vacuo the residue chromatographed on silica gel eluting with ether/petrol (60-80)

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

Procedure: A stirred solution of ethyl piperidin-2-ylacetate (8.0 g, 0.047 mole) and ethyl 4-bromobutyrate (6.7 ml, 0.047 mole) in acetone (100 ml) was treated with potassium carbonate (13 g, 0.094 mole) and heated under reflux for 32 h. A further 1.5 ml of ethyl 4-bromobutyrate and 3 g of potassium carbonate was added and reflux continued for 16 h. The mixture was concentrated in vacuo and the residue treated with water (100 ml) and extracted with ethyl acetate (2×100 ml). The combined extracts were dried (Na2SO4), concentrated in vacuo and the residue chromatographed on silica gel eluting with ether/petrol (60-80) to afford the title compound as a pale yellow oil (11.5 g, 86%) heated under reflux for 32 h reflux The mixture was concentrated in vacuo the residue treated with water (100 ml) extracted with ethyl acetate (2×100 ml) The combined extracts were dried (Na2SO4) concentrated in vacuo the residue chromatographed on silica gel eluting with ether/petrol (60-80)

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

Procedure: At rt a mixture of ethyl 2-(pyridin-2-yl)acetate (3.0 g, 18 mmol) and platinum (IV) oxide (0.825 g, 3.63 mmol) in methanol (25 mL) was subject to hydrogenation at 50 psi for 18 h. After filtration, the filtrate was concentrated to afford Intermediate 22A (3.0 g, 96%) as a clear oil. HPLC/MS (Method L) RT=0.99 min, [M+1]+ 172.2. After filtration the filtrate was concentrated

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

Procedure: 50 ml of ethyl 2-(2-pyridyl)acetate, 18.7 ml of acetic acid, 5 g of Pd—C (water-containing product) and 200 ml of ethanol were charged in an auto clave, and the mixture was stirred at 70° C. for 9 hours at a hydrogen pressure of 56 kg/cm2. The Pd—C was filtered off and ethanol was evaporated, to give 72.3 g of white crystals. The Pd—C was filtered off ethanol was evaporated

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

Procedure: Platinum(IV) oxide (15 mg) was added to a mixture of 2-(2-pyridyl)acetic acid ethyl ester (1.652 g) in water (1.25 mL) and concentrated hydrochloric acid (1.25 mL) in methanol (15 mL), and the resultant mixture was stirred in a hydrogen atmosphere at room temperature for 15 hours. The catalyst was filtered off. The solvent was evaporated under reduced pressure, and ethanol was added to the residue, and then the solvent of the mixture was evaporated again under reduced pressure. To the residue, a small amount of water, diethyl ether (about 100 mL), and an excessive amount of potassium carbonate were added, and the resultant mixture was stirred, followed by filtration. The solvent of the filtrate was evaporated under reduced pressure, to thereby give the title compound as an oily product (1.322 g, 77%). The catalyst was filtered off The solvent was evaporated under reduced pressure, and ethanol was added to the residue the solvent of the mixture was evaporated again under reduced pressure To the residue, a small amount of water, diethyl ether (about 100 mL), and an excessive amount of potassium carbonate were added followed by filtration The solvent of the filtrate was evaporated under reduced pressure

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

Procedure: A stirred solution of ethyl piperidin-2-ylacetate (8.0 g, 0.047 mole) and ethyl 4-bromobutyrate (6.7 ml, 0.047 mole) in acetone (100 ml) was treated with potassium carbonate (13 g, 0.094 mole) and heated under reflux for 32 h. A further 1.5 ml of ethyl 4-bromobutyrate and 3 g of potassium carbonate was added and reflux continued for 16 h. The mixture was concentrated in vacuo and the residue treated with water (100 ml) and extracted with ethyl acetate (2×100 ml). The combined extracts were dried (Na2SO4), concentrated in vacuo and the residue chromatographed on silica gel eluting with ether/petrol (60-80) to afford the title compound as a pale yellow oil (11.5 g, 86%) heated under reflux for 32 h reflux The mixture was concentrated in vacuo the residue treated with water (100 ml) extracted with ethyl acetate (2×100 ml) The combined extracts were dried (Na2SO4) concentrated in vacuo the residue chromatographed on silica gel eluting with ether/petrol (60-80)