Sodium hydride → Benzyl 4-((1R,2S)-2-{2-[(3-methyl-5-nitropyridin-2-yl)oxy]ethyl}cyclopropyl)piperidine-1-carboxylate

To the solution of benzyl 4-[(1R,2S)-2-(2-hydroxyethyl)cyclopropyl)piperidine-1-carboxylate (3.0 g, 9.89 mmol) in 10 ml of anhydrous DMF was added NaH (0.40 g, 9.89 mmol) in small portions at RT and the final resulting solution was stirred for 15 min. Commercially available 2-chloro-3-methyl-5-nitropyridine (1.37 g, 7.91 mmol) was added in 10 portions over 2 minutes and the resulting mixture was stirred 3 hrs at RT. The reaction mixture was quenched with ice cooled aqueous sat'd NH4Cl solution and extracted with ethyl acetate/ether (1:1) (2×50 mL). The organics were combined, dried over sodium sulfate, filtered, and the filtrate concentrated under reduced pressure. The residue was purified on Biotage column (40M+ silica gel) using a gradient eluant of 0-60% ethyl acetate in hexane (800 ml) to afford the title compound. LC/MS (m/z): 440 (M+H)+.

1. customthe final resulting solution
2. stirringthe resulting mixture was stirred 3 hrs at RT
3. customThe reaction mixture was quenched with ice cooled aqueous sat'd NH4Cl solution
4. extractionextracted with ethyl acetate/ether (1:1) (2×50 mL)
5. dry with materialdried over sodium sulfate
6. filtrationfiltered
7. concentrationthe filtrate concentrated under reduced pressure
8. customThe residue was purified on Biotage column (40M+ silica gel)

ORD record

ord-431acc22d41b4c1680000f193ff3ea51

Source dataset

uspto-grants-2015_02

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US08957062B2