Cesium carbonate → 3-[(R*)-1-[(S)-1-(2,3-Dihydro-benzo[1,4]dioxin-2-yl)methyl]-piperidin-3-yl]-phenylamine

Temperature

80 °C

A mixture of trifluoro-methanesulfonic acid 3-{(R*)-1-[(S)-1-(2,3-dihydro-benzo[1,4]dioxin-2-yl)methyl]-piperidin-3-yl}-phenyl ester (1.039 g, 2.27 mmol), cesium carbonate (1.036 g, 3.18 mmol), palladium acetate (0.015, 0.068 mmol), (R)-(±)-2,2-bis(diphenylphosphino)-1,1-binaphthyl (0.064 g, 0.102 mmol) and benzophenone imine (0.457 ml, 2.73 mmol) in dry tetrahydrofuran (6 ml) was heated in a microwave reactor at 80° C. for 10 hours. The mixture was filtered and evaporated to dryness. The crude product was purified by flash chromatography using a gradient of heptane and EtOAc as eluent. The residue on evaporation was dissolved in dry methanol, sodium acetate (0.54 g, 6.55 mmol) and hydroxylamine hydrochloride (0.36 g, 5.24 mmol) was added and the mixture was stirred at room temperature for 1.5 h. The mixture was evaporated to dryness, dissolved in EtOAc and washed with 1M Na2CO3. The organic layer was dried (Na2SO4), filtered and evaporated to dryness. The crude product was purified by flash chromatography using gradient of heptane and EtOAc as eluent to give 151 mg of the title compound.

1. filtrationThe mixture was filtered
2. customevaporated to dryness
3. customThe crude product was purified by flash chromatography
4. customThe residue on evaporation
5. dissolutionwas dissolved in dry methanol
6. customThe mixture was evaporated to dryness
7. dissolutiondissolved in EtOAc
8. washwashed with 1M Na2CO3
9. dry with materialThe organic layer was dried (Na2SO4)
10. filtrationfiltered
11. customevaporated to dryness
12. customThe crude product was purified by flash chromatography

ORD record

ord-7721b85562094cb387b0c15b03385024

Source dataset

uspto-grants-2014_08

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US08809536B2