Triphenylphosphine → 3-(5-bromo-6-fluoropyridin-2-yl)oxy-N,N-dimethylpropan-1-amine

Temperature

2.5 °C

(E)-Diisopropyl diazene-1,2-dicarboxylate (15.80 g, 78.13 mmol) was added drop wise to 3-(dimethylamino)propan-1-ol (8.06 g, 78.13 mmol), 5-bromo-6-fluoropyridin-2-ol (10 g, 52.09 mmol) and triphenylphosphine (20.49 g, 78.13 mmol) in DCM (150 mL) cooled to 0-5° C. under an inert atmosphere. The resulting solution was stirred at ambient temperature for 16 h then the solvent, removed under reduced pressure. The residue was diluted with EtOAc (50 mL) and the solid removed by filtration and discarded. The filtrate was acidified with hydrogen chloride in dioxane. The solid was collected by filtration then dissolved in a sat. aqueous solution of Na2CO3 (200 mL) and extracted with EtOAc (3×100 mL). The combined organic layers were washed with water, brine, dried over Na2SO4 and concentrated in vacuo to afford the desired material (9.00 g, 62.3%). NMR Spectrum: 1H NMR (300 MHz, CDCl3) δ 1.89-1.98 (2H, m), 2.26 (6H, s), 2.34 (2H, t), 4.30 (2H, t), 6.53 (1H, d), 7.74 (1H, t). Mass Spectrum: m/z (ES+)[M+H]+=277.

1. customthe solvent, removed under reduced pressure
2. additionThe residue was diluted with EtOAc (50 mL)
3. customthe solid removed by filtration
4. filtrationThe solid was collected by filtration
5. dissolutionthen dissolved in a sat. aqueous solution of Na2CO3 (200 mL)
6. extractionextracted with EtOAc (3×100 mL)
7. washThe combined organic layers were washed with water, brine
8. dry with materialdried over Na2SO4
9. concentrationconcentrated in vacuo

ORD record

ord-7d743d6cbf834d7daeaba91bc29e1d3f

Source dataset

uspto-grants-2016_08

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US09428503B2