Sodium hydride → (4-[(R)-2-(1-ethoxy-ethoxymethyl)-6-oxo-piperidin-1-yl]-but-2-ynyloxy}-acetic acid methyl ester

Participants

Reaction Steps

Sodium hydride (60% dispersion in oil, 278 mg, 6.95 mmol) was added to a solution of (R)-6-(1-ethoxyethoxymethyl)piperidin-2-one (from example 1, step 1, 1.40 g, 6.96 mmol) in DMF (10 mL) at 0° C. After 1 h at 0° C., (4-iodo-but-2-ynyloxy)-acetic acid methyl ester (2.05 g, 7.65 mmol) in DMF (10 mL) was added via cannula and the reaction was allowed to warm to rt. After 15 min at rt, the reaction mixture solidified, so more DMF (3 mL) was added. After 18 h at rt, the reaction was treated with saturated aqueous NaHCO3 (50 mL) and extracted with EtOAc (3×70 mL). The combined extracts were washed with water (2×50 mL) and brine (2×50 mL) then dried (MgSO4), filtered and concentrated in vacuo. Purification of the residue by flash column chromatography on silica gel (20%→50% EtOAc/CH2Cl2, gradient) afforded 500 mg (21%) of {4-[(R)-2-(1-ethoxy -ethoxymethyl)-6-oxo-piperidin-1-yl]-but-2-ynyloxy}-acetic acid methyl ester.

Provenance & Evidence