Water → (1R,5S)-3-(3-chloropropyl)-N,N-dimethyl-3-azabicyclo[3.1.0]hexan-1-amine

Temperature

65 °C

To a solution of (1R,5S)-3-benzyl-N,N-dimethyl-3-azabicyclo[3.1.0]hexan-1-amine (0.28 g, 1.29 mmol) in MeOH (20 mL) was added 20% Pd(OH)2 (30 mg). The mixture was stirred at rt under H2 overnight and filtered. The filtrate was concentrated in vacuo to give the crude product (1R,5S)—N,N-dimethyl-3-azabicyclo[3.1.0]hexan-1-amine (0.16 g), which was used for the next step without further purification. To a solution of (1R,5S)—N,N-dimethyl-3-azabicyclo[3.1.0]hexan-1-amine in acetone (5 mL) was added anhydrous K2CO3 (0.35 g, 2.54 mmol, 2.0 eq) and 1-bromo-3-chloropropane (0.20 mL, 1.91 mmol, 1.5 eq) in turn. The reaction mixture was heated at 65° C. for 4 h, and then cooled to rt. To the reaction mixture was added water (5 mL) and the mixture was extracted with EtOAc (10 mL×3). The combined organic phases were washed with water and brine, dried over anhydrous Na2SO4 and filtered. The filtrate was concentrated in vacuo and the residue was purified by a silica gel column chromatography (30:1 (v/v) CHCl3/CH3OH) to give the title compound as colorless oil (103 mg, 40%). The compound was characterized by the following spectroscopic data: MS (ESI, pos. ion) m/z: 203.2 (M+1).

1. customwas used for the next step without further purification
2. temperaturecooled to rt
3. extractionthe mixture was extracted with EtOAc (10 mL×3)
4. washThe combined organic phases were washed with water and brine
5. dry with materialdried over anhydrous Na2SO4
6. filtrationfiltered
7. concentrationThe filtrate was concentrated in vacuo
8. customthe residue was purified by a silica gel column chromatography (30:1 (v/v) CHCl3/CH3OH)

ORD record

ord-b10f431d2bb845bc936e3403e7a62dc9

Source dataset

uspto-grants-2015_11

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US09181277B2