N-Boc-hexahydro-1H-azepin-4-one → tert-Butyl 4-methylideneazepane-1-carboxylate

Temperature

-78 °C

A solution of 1 g methyltriphenylphosphoniumbromide (MW: 357.22, 2.79 mmol) in 20 ml of tetrahydrofurane was treated at −78° C. with 1.22 ml of a 2.3 M n-butyl lithium solution in N-hexane (2.8 mmol). The reaction mixture was stirred at −78° C. for ten minutes, then at 0° C. for one hour. The yellow suspension was cooled to −78° C. and treated with a solution of 595 mg 4-oxo-azepane-1-carboxylic acid tert-butyl ester (WO 2000044376) (MW: 213.279, 2.78 mmol) in 10 ml tetrahydrofurane. The reaction mixture was stirred at room temperature for one and half hour. The reaction mixture was quenched with 30 ml of a saturated aqueous solution of ammonium chloride, diluted with 30 ml of ethyl acetate. The organic layer was successively washed with 30 ml water and 30 ml brine, dried over magnesium sulfate and filtered. The filtrate was evaporated under reduced pressure and the residue purified by chromatography over silica. (cyclohexane:ethyl acetate 1:1). Yield: 487 mg, 83%. NMR (CDCl3): 1.35 ppm (s, 9H, tert-but.); 1.6 ppm (m, 2H, —CH2—), 2.14 ppm (m, 2H), 2.33 ppm (m, 2H); 3.29 ppm (m, 4H, N—CH2); 4.67 ppm (m, 2H, vinyl-CH2).

1. temperatureThe yellow suspension was cooled to −78° C.
2. stirringThe reaction mixture was stirred at room temperature for one and half hour
3. customThe reaction mixture was quenched with 30 ml of a saturated aqueous solution of ammonium chloride
4. additiondiluted with 30 ml of ethyl acetate
5. washThe organic layer was successively washed with 30 ml water and 30 ml brine
6. dry with materialdried over magnesium sulfate
7. filtrationfiltered
8. customThe filtrate was evaporated under reduced pressure
9. customthe residue purified by chromatography over silica

ORD record

ord-26da727f808648b5832e771f67b00f77

Source dataset

uspto-grants-2012_09

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US08268812B2