N,O-Dimethylhydroxylamine → tert-Butyl 4-(methoxy(methyl)carbamoyl)piperidine-1-carboxylate

N,O-dimethylhydroxylamine hydrochloride (851 mg, 8.72 mmols) was suspended in dichloromethane (6 ml) and cooled to 0 C. N,N′-diisopropylethylamine (1.66 ml, 9.53 mmols) was added and the mixture was stirred at 0 C until a clear solution was obtained. The resulting solution was kept at 0 C for further use. Boc-isonipecotic acid (2 g, 8.72 mmol), 1-hydroxybenzotriazole (1.2 g, 8.88 mmols) and 1-(3-dimethylaminopropyl)-3-ethylcarbodiimide hydrochloride (EDCl) (1.83 g, 9.58 mmols) were dissolved in DMF (15 ml) and cooled to 0 C. The solution of N,O-dimethylhydroxylamine in dichloromethane was added with stirring, and the resulting reaction mixture was allowed to stir overnight at room temperature. DMF was removed under reduced pressure and residue was partitioned between ethyl acetate and 10% citric acid. Organic layer was isolated, washed with water, saturated NaHCO3, water and brine and dried over MgSO4. Solvent was removed under reduced pressure and the residue was purified on silica gel eluting with ethyl acetate in hexanes (2:1) to provide the title compound (1.88 g, 79%). LCMS m/e (295, M+Na).

1. temperaturecooled to 0 C
2. customwas obtained
3. temperaturecooled to 0 C
4. stirringwith stirring
5. customthe resulting reaction mixture
6. stirringto stir overnight at room temperature
7. customDMF was removed under reduced pressure and residue
8. customwas partitioned between ethyl acetate and 10% citric acid
9. customOrganic layer was isolated
10. washwashed with water, saturated NaHCO3, water and brine
11. dry with materialdried over MgSO4
12. customSolvent was removed under reduced pressure
13. customthe residue was purified on silica gel eluting with ethyl acetate in hexanes (2:1)

ORD record

ord-a64c933a35fa4f8cba8d200873faae6e

Source dataset

uspto-grants-2013_10

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US08546404B2