Potassium Iodide → {(Z)-4-[(R)-2-(1-ethoxyethoxymethyl)-6-oxo-piperidin-1-yl]-but-2-enyloxy}-acetic acid ethyl ester

Sodium hydride (60% dispersion in oil, 402 mg, 10.0 mmol) was added to a solution of (R)-6-(1-ethoxyethoxymethyl)-piperidin-2-one (2.02 g, 10.0 mmol) in DMF (15 mL) at 0° C. After 1 h, a solution of potassium iodide (1.66 g, 10.0 mmol) and ((Z)-4-chloro-but-2-enyloxy)-acetic acid ethyl ester (prepared according to PCT 2003/007941, 3.09 g, 16.0 mmol) in DMF (10 mL) was added via cannula. The reaction was allowed to warm to rt. After 18 h at rt, the reaction was quenched by the addition of saturated aqueous NaHCO3 (100 mL) and the mixture was extracted with EtOAc (3×100 mL). The combined organic phase was washed with brine (3×100 mL), dried (Na2SO4), filtered and concentrated in vacuo. Purification of the residue by flash column chromatography on silica gel (10% EtOAc/CH2Cl2→60% EtOAc/CH2Cl2, gradient) afforded 1.10 g (31%) of {(Z)-4-[(R)-2-(1-ethoxyethoxymethyl)-6-oxo-piperidin-1-yl]-but-2-enyloxy}-acetic acid ethyl ester.

1. waitAfter 18 h at rt
2. customthe reaction was quenched by the addition of saturated aqueous NaHCO3 (100 mL)
3. extractionthe mixture was extracted with EtOAc (3×100 mL)
4. washThe combined organic phase was washed with brine (3×100 mL)
5. dry with materialdried (Na2SO4)
6. filtrationfiltered
7. concentrationconcentrated in vacuo
8. customPurification of the residue by flash column chromatography on silica gel (10% EtOAc/CH2Cl2→60% EtOAc/CH2Cl2, gradient)

ORD record

ord-a0fbf140a1804e3cb4989f725488556b

Source dataset

uspto-grants-2007_02

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US07179820B2