Benzoyl Peroxide → HCID 66600183, compound

Temperature

80 °C

A solution of 3-bromo-2-fluoro-6-methylpyridine (1.44 g, 7.58 mmol) (Waterstone Technology) in carbon tetrachloride (15 mL) was treated with N-bromosuccinimide (1.42 g, 7.96 mmol) and dibenzoyl peroxide (184 mg, 0.758 mmol) and heated in an oil bath at 80° C. for 2 h, when LCMS detected a mixture of starting material, mono- and bis-brominated products. The reaction mixture was cooled to RT and filtered through a fritted funnel The filtrate was concentrated and the resulting brown oil was purified on a Redi-Sep pre-packed silica gel column (40 g) eluting with a gradient of 1-20% EtOAc in hexanes to give a thick oil containing a mixture of starting material, mono- and bis-brominated products. The residue was dissolved in 5 mL of DMF at 0° C., treated with morpholine (0.715 mL, 8.21 mmol) and potassium carbonate (1.1 g, 7.70 mmol), and stirred at 0° C. for 45 min. Icy water (10 mL) was added and stirred at RT for 15 min. The off-white solid was filtered, rinsed with 2×5 mL of water and collected. The solid was dried in a vacuum oven at 40° C. for 48 h to yield 268 mg of 4-((5-bromo-6-fluoropyridin-2-yl)methyl)morpholine. The filtrate was transferred to a separatory funnel and extracted with 2×50 mL of EtOAc. The EtOAc solution was washed with brine, dried and concentrated. The residue was purified on a Redi-Sep pre-packed silica gel column (40 g) eluting with a gradient of 50-75% EtOAc in hexanes to give 432 mg of 4-((5-bromo-6-fluoropyridin-2-yl)methyl)morpholine. 1H NMR (400 MHz, d6-DMSO) δ 8.26 (1H, m); 7.36 (1H, dd, J=7.8, 1.4 Hz); 3.58 (4H, t, J=4.3 Hz); 3.52 (2H, s); 2.41 (4H, t, J=4.3 Hz). m/z (ESI, +ve ion) 275/277 (M+H)+.

1. additiona mixture of starting material
2. temperatureThe reaction mixture was cooled to RT
3. filtrationfiltered through a fritted funnel The filtrate
4. concentrationwas concentrated
5. customthe resulting brown oil was purified on a Redi-Sep pre-packed silica gel column (40 g)
6. washeluting with a gradient of 1-20% EtOAc in hexanes
7. customto give a thick oil
8. additioncontaining
9. additiona mixture of starting material
10. stirringstirred at RT for 15 min
11. filtrationThe off-white solid was filtered
12. washrinsed with 2×5 mL of water
13. customcollected
14. customThe solid was dried in a vacuum oven at 40° C. for 48 h

ORD record

ord-f9a412ec76234fa5bd12c8726ddc601e

Source dataset

uspto-grants-2013_01

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US08362241B2