Sodium hydride → Hept-5-ynoic acid methyl ester

Sodium hydride (60% dispersion in oil, 195 mg, 4.87 mmol) was added to a solution of (R)-6-(tert-butyldimethylsilanyloxymethyl)-piperidin-2-one (1.13 g, 4.64 mmol) in DMF (8 mL) at rt. After 1 h, methyl 7-iodohept-5-ynoate (1.35 g, 5.07 mmol) in DMF (2 mL) was added via cannula. After 18 h at rt, the reaction was quenched by the addition of aqueous HCl (0.5 M, 25 mL) and the mixture was extracted with EtOAc (3×50 mL). The combined organic phase was washed with saturated aqueous NaHCO3 (50 mL) and brine (3×50 mL), dried (Na2SO4), filtered and concentrated in vacuo. Purification of the residue by flash column chromatography on silica gel (CH2Cl2→50% EtOAc/CH2Cl2, gradient) afforded 713 mg (40%) of 7-[(R)-2-tert-butyldimethylsilanyloxymethyl)-6-oxo-piperidin-1-yl]-hept-5-ynoic acid methyl ester.

1. waitAfter 18 h at rt
2. customthe reaction was quenched by the addition of aqueous HCl (0.5 M, 25 mL)
3. extractionthe mixture was extracted with EtOAc (3×50 mL)
4. washThe combined organic phase was washed with saturated aqueous NaHCO3 (50 mL) and brine (3×50 mL)
5. dry with materialdried (Na2SO4)
6. filtrationfiltered
7. concentrationconcentrated in vacuo
8. customPurification of the residue by flash column chromatography on silica gel (CH2Cl2→50% EtOAc/CH2Cl2, gradient)

ORD record

ord-7a39aed66fa240b595788cd3e596a335

Source dataset

uspto-grants-2008_02

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US07326716B2