Acetyl chloride → HCID 69019214, compound

Temperature

90 °C

To a solution of 7.5 g (16.8 mmol) of 3-4 in 50 mL of pyridine was added 1.22 mL (25.2 mmol) hydrazine hydrate, and the resulting mixture was heated at 90° C. for 30 min. After cooling to room temperature, the reaction was placed in an ice bath and 5.96 mL (83.8 mmol) acetyl chloride was added dropwise. The bath was removed and the reaction was stirred overnight at room temperature before being dumped into a separatory funnel containing EtOAc and brine. The layers were separated, the organic was washed twice with 1M HCl, once with brine, dried over Na2SO4, and concentrated by rotary evaporation. The residue was twice resuspended in toluene and concentrated to azeotrope off any remaining pyridine. The residue was dissolved in 200 mL of MeOH and ˜2 g of p-toluenesulfonic acid monohydrate was added. After stirring for 2 h at room temperature, most of the solvent was removed by rotary evaporation and the residue was partitioned between saturated aqueous NaHCO3 and EtOAc. After separating the layers, the organic was washed again with NaHCO3, then brine, dried over Na2SO4, and concentrated by rotary evaporation. The residue was purified by silica gel chromatography with EtOAc/hexanes to provide 3-5 as a white solid. Data for racemic 3-5: 1HNMR (500 MHz, CDCl3) δ 8.15 (m, 1H), 7.4-7.2 (m, 6H), 7.0 (m, 1H), 3.8-3.7 (m, 2H), 3.6 (m, 1H), 3.45 (m, 1H), 2.9 (m, 1H), 2.45 (s, 3H), 2.3 (m, 1H), 1.7-1.5 (m, 2H) ppm. HRMS (ES) calc'd M+H for C20H20BrFN2O2: 419.0765. Found: 419.0769.

1. temperatureAfter cooling to room temperature
2. customthe reaction was placed in an ice bath
3. customThe bath was removed
4. custombefore being dumped into a separatory funnel
5. additioncontaining EtOAc and brine
6. customThe layers were separated
7. washthe organic was washed twice with 1M HCl, once with brine
8. dry with materialdried over Na2SO4
9. concentrationconcentrated by rotary evaporation
10. concentrationconcentrated
11. dissolutionThe residue was dissolved in 200 mL of MeOH
12. addition˜2 g of p-toluenesulfonic acid monohydrate was added
13. stirringAfter stirring for 2 h at room temperature, most of the solvent
14. customwas removed by rotary evaporation
15. customthe residue was partitioned between saturated aqueous NaHCO3 and EtOAc
16. customAfter separating the layers
17. washthe organic was washed again with NaHCO3
18. dry with materialbrine, dried over Na2SO4
19. concentrationconcentrated by rotary evaporation
20. customThe residue was purified by silica gel chromatography with EtOAc/hexanes

ORD record

ord-ee9654763ac548d5bcc1a9e9cf9e1514

Source dataset

uspto-grants-2009_12

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US07625936B2