Phenol → (1S)-1-(3-phenoxyphenyl)ethan-1-amine

Temperature

90 °C

Into a 20 ml microwave vial was weighted 1-(pyridin-2-yl)propan-2-one ligand (90 mg, 0.665 mmol), phenol (407 mg, 4.32 mmol), CuBr (47.7 mg, 0.332 mmol) and Cs2CO3 (2166 mg, 6.65 mmol). To the mixture was added DMSO (5 ml) and (S)-1-(3-bromophenyl)ethanamine (0.5 ml, 3.32 mmol). The tube was flushed with N2, capped, and the black mixture heated in the oil bath at 90° C. for 18 hours. The heterogenous mixture was diluted with EtOAc and filtered through a glass-fritted funnel, eluting with EtOAc and another 5 mls of DMSO. The volatiles were then removed in vacuo and the crude brown liquid was filtered through 1 um PTFE filter and purified by reverse phase HPLC. The combined product fractions were desalted by addition of equal amount of EtOAc and about 250 mg Na2CO3 in a separatory funnel. The phases were separated and the organic washed with brine, dried over MgSO4, filtered and concentrated in vacuo to yield (S)-1-(3-phenoxyphenyl)ethanamine (361.5 mg, 1.678 mmol, 50.5% yield) as an amber oil. LCMS m/z 214.1 (M+H)+, Rt 0.61 min.

1. customThe tube was flushed with N2
2. customcapped
3. additionThe heterogenous mixture was diluted with EtOAc
4. filtrationfiltered through a glass-fritted funnel
5. washeluting with EtOAc
6. customThe volatiles were then removed in vacuo
7. filtrationthe crude brown liquid was filtered through 1 um PTFE
8. filtrationfilter
9. custompurified by reverse phase HPLC
10. additionThe combined product fractions were desalted by addition of equal amount of EtOAc and about 250 mg Na2CO3 in a separatory funnel
11. customThe phases were separated
12. washthe organic washed with brine
13. dry with materialdried over MgSO4
14. filtrationfiltered
15. concentrationconcentrated in vacuo

ORD record

ord-327ccacb149a47d1b5aaa45de1a3b243

Source dataset

uspto-grants-2016_09

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US09434719B2