1-Hydroxybenzotriazole → N-Methoxy-N,1-dimethylpiperidine-4-carboxamide

1-Methylisonipecotic acid (5.5 g, 38.4 mmol) was dissolved in dimethylformamide (100 ml) with heating. Diisopropylethylamine (8.0 ml, 46.1 mmol), 1-hydroxybenzotriazole (5.2 g, 38.4 mmol), and N,O-dimethylhydroxylamine hydrochloride (4.1 g, 42.2 mmol) were added and the reaction mixture was stirred 5 min. 1-(3-dimethylaminopropyl)-3-ethylcarbodiimide hydrochloride (7.4 g, 38.4 mmol) was added and the resulting homogeneous solution was stirred for 63 hours at ambient temperature. The solvent was removed under reduced pressure. The residue was dissolved in water and the solution was basified to pH 9 with 5N sodium hydroxide solution. This aqueous solution was extracted with methylene chloride then saturated with sodium chloride and extracted with chloroform/isopropanol (3/1). The combined organic extracts were dried over sodium sulfate and the solvent was removed under reduced pressure to give 9.5 g of a yellow liquid. Purification by flash chromatography (silica gel, methylene chloride:methanol:ammonium hydroxide, 100:10:1) gave 5.7 g (80%) of product as a light yellow liquid.

1. temperaturewith heating
2. stirringthe resulting homogeneous solution was stirred for 63 hours at ambient temperature
3. customThe solvent was removed under reduced pressure
4. dissolutionThe residue was dissolved in water
5. extractionThis aqueous solution was extracted with methylene chloride
6. extractionsaturated with sodium chloride and extracted with chloroform/isopropanol (3/1)
7. dry with materialThe combined organic extracts were dried over sodium sulfate
8. customthe solvent was removed under reduced pressure

ORD record

ord-53140686daec4dd182c1882fdbaa661d

Source dataset

uspto-grants-2004_08

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US06777428B1