methyl 2-(4-hydroxypiperidin-1-yl)acetate

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 title compound can be prepared in accordance with the general method of intermediate B, step 3 from (4-hydroxy-piperidin-1-yl)-acetic acid methyl ester.

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

Procedure: Treat a solution of (4-hydroxy-piperidin-1-yl)-acetic acid methyl ester (10.0 g, 57.7 mmol) and imidazole (4.71 g, 69.2 mmol) in DMF (100 mL) with t-butyl-diphenylsilyl chloride (19.04 g, 69.3 mmol) and stir for 16 hours at room temperature. Dilute the reaction with diethyl ether and wash with water. Dry the organic layer (Na2SO4), remove the solvent in vacuo to afford crude product, and purify with a 2% methanol in CH2Cl2 to afford 17.38 g (73%) of the titled product. Rf=0.71 (9/1 CH2Cl2/methanol). ES MS (m/z): 412 (M+). Dilute wash with water Dry the organic layer (Na2SO4) remove the solvent in vacuo to afford crude product purify with a 2% methanol in CH2Cl2

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

Procedure: Treat a 0° C. solution of 4-hydroxy-piperidine (20.0 g, 0.19 mol) and (CH3CH2)3N (24.0 g, 0.24 mol) in CH2Cl2 (200 mL) with methyl bromoacetate (30.21 g, 0.197 mol), warm to room temperature, and stir 2 hours at room temperature under N2. Dilute the reaction with water and extract with 3:1 chloroform:isopropanol. Dry the organic layer (Na2SO4), remove the solvent in vacuo to afford crude product, and purify with a 5% methanol in CH2Cl2 to afford 20.13 g (59%) of the titled product. Rf=0.13 (9/1 CH2Cl2/methanol). ES MS (m/z): 174 (M+). Dilute extract with 3:1 chloroform Dry the organic layer (Na2SO4) remove the solvent in vacuo to afford crude product purify with a 5% methanol in CH2Cl2