Acetic Acid → Tert-butyl 4-(2-(((trans)-2-phenylcyclopropyl)amino)ethyl)piperidine-1-carboxylate

To a solution of tert-butyl 4-(2-oxoethyl)piperidine-1-carboxylate (1 g, 4.40 mmol) in methanol (15 mL) were added (trans)-2-phenylcyclopropanamine (0.762 g, 5.72 mmol) and acetic acid (0.252 mL, 4.40 mmol), and the mixture was stirred at room temperature for 1 h. Sodium cyanoborohydride (0.415 g, 6.60 mmol) was added and the mixture was stirred at room temperature for 18 h. The reaction was quenched with water (10 mL) and the mixture was concentrated to remove methanol. The resulting aqueous layer was extracted with DCM (3×). The DCM extract was washed with 10% HOAc aqueous solution, dried (Na2SO4) and concentrated. The residue was purified using column chromatography (silica gel, 0 to 100% EtOAc/hexanes) to give 720 mg of product as pale yellow oil. MS: (M+H)+=345.4. 1H NMR (400 MHz, CHLOROFORM-d) δ ppm 0.94-1.75 (m, 18H), 1.86-1.95 (m, 1H), 2.35 (dt, J=7.01, 3.69 Hz, 1H), 2.60-2.86 (m, 4H), 4.08 (br. s., 2H), 6.91-7.38 (m, 5H).

1. stirringthe mixture was stirred at room temperature for 18 h
2. customThe reaction was quenched with water (10 mL)
3. concentrationthe mixture was concentrated
4. customto remove methanol
5. extractionThe resulting aqueous layer was extracted with DCM (3×)
6. extractionThe DCM extract
7. washwas washed with 10% HOAc aqueous solution
8. dry with materialdried (Na2SO4)
9. concentrationconcentrated
10. customThe residue was purified

ORD record

ord-818baa0299e24489b35e50c100a5fe38

Source dataset

uspto-grants-2014_10

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US08853408B2