1,1,1-Trichloroethane → HCID 18420200, compound

A mixture of 2-ethylpyridine (20.0 g, 187 mmol), N-bromosuccinimide (38.0 g, 213 mmol), and benzoyl peroxide (1.0 g, 75% in water) in 1,1,1-trichloroethane (200 ml), was heated under reflux for 3 hours. The cooled mixture was filtered, and the filtrate washed with water (2×100 ml), aqueous sodium thiosulphate solution (100 ml), and brine (100 ml). The solution was dried (MgSO4), filtered through charcoal, and then hydrobromic acid (25 ml, 62%) added. This solution was concentrated under reduced pressure and azeotroped with toluene to give 2-(1-bromoethyl)pyridine hydrochloride as a dark oil (66.0 g). A mixture of the title compound of Preparation 35 (8.0 g, 43.4 mmol), caesium carbonate (35.0 g, 107.4 mmol) and the crude 2-(1-bromoethyl)pyridine hydrochloride (13.6 g, 52.0 mmol) in N,N-dimethylformamide (80 ml) was stirred at room temperature for 20 hours. The mixture was concentrated under reduced pressure and the residue partitioned between ethyl acetate (150 ml) and water (50 ml). The layers were separated and the organic phase washed with more water (3×50 ml), brine (50 ml), then dried (MgSO4) and evaporated under reduced pressure. The residual oil was purified by column chromatography on silica gel, using an elution gradient of pentane: ethyl acetate: methanol (90:10:0 to 0:100:0 to 0:90:10) to afford the N1 isomer (4.3 g), and the title compound (5.7 g, 45%). δ (CDCl3): 1.14 (3H, t), 2.01 (3H, d), 3.00 (2H, q), 5.66 (2H, q 5.88 (1H, s), 6.98 (1H, s), 7.18 (1H, d), 7.25 (1H, m), 7.68 (1H, m), 8.56 (1H, d). LRMS: m/z 290 (M+1)+

1. temperaturewas heated
2. temperatureunder reflux for 3 hours
3. filtrationThe cooled mixture was filtered
4. washthe filtrate washed with water (2×100 ml), aqueous sodium thiosulphate solution (100 ml), and brine (100 ml)
5. dry with materialThe solution was dried (MgSO4)
6. filtrationfiltered through charcoal
7. additionhydrobromic acid (25 ml, 62%) added
8. concentrationThis solution was concentrated under reduced pressure
9. customazeotroped with toluene

ORD record

ord-d63712c11cf149928d1bf1681fe5224c

Source dataset

uspto-grants-2001_06

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US06251904B1