Bromoacetic Acid → 2-((1-((Tert-butoxy)carbonyl)piperidin-4-yl)oxy)acetic acid

Sodium hydride (596 mg of a 60% dispersion in oil, 14.9 mmol) was added portionwise to a stirred solution of tert-butyl-4-hydroxypiperidine-1-carboxylate (1.0 g, 5 mmol) in anhydrous THF (20 ml) at rt. After 15 min, bromoacetic acid (1.38 g, 9.94 mmol) was introduced and stirring continued for 5 h. Additional bromoacetic acid (5 mmol) and sodium hydride (5 mmol) were added and stirring continued for 24 h. The reaction was quenched with water (2 ml) and diluted with EtOAc (20 ml), which was washed with saturated aqueous NaHCO3 (20 ml). Using dilute HCl, the aqueous phase was acidified to pH 2 and the precipitate extracted into EtOAc (50 ml). The organic phase was dried (MgSO4), evaporated and the residue was purified by flash chromatography (5% AcOH in IH-EtOAc, 7:3 to 1:1) to afford the title acid: RT=2.89 min; m/z (ES+)=260.3 [M+H]+.

1. waitcontinued for 5 h
2. stirringstirring
3. waitcontinued for 24 h
4. customThe reaction was quenched with water (2 ml)
5. additiondiluted with EtOAc (20 ml), which
6. washwas washed with saturated aqueous NaHCO3 (20 ml)
7. extractionthe precipitate extracted into EtOAc (50 ml)
8. dry with materialThe organic phase was dried (MgSO4)
9. customevaporated
10. customthe residue was purified by flash chromatography (5% AcOH in IH-EtOAc, 7:3 to 1:1)

ORD record

ord-290d2a1728b148959101268ec10b84cf

Source dataset

uspto-grants-2012_06

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US08207147B2