Hydrochloric Acid → HCID 90072119, compound

Temperature

-78 °C

In a 500 mL round-bottomed flask a solution of 1-fluoro-3-iodobenzene (13.61 mL, 116 mmol) in THF (120 mL) was cooled in −78° C. bath. A solution BuLi, 2.5M in hexane (46.3 mL, 116 mmol) was added dropwise over 10 minutes to give a slightly cloudy yellow solution. The solution was stirred at −78° C. for 30 minutes and then treated with a solution of 2-amino-N-methoxy-N,3-dimethylbenzamide (6.43 g, 33.1 mmol) in THF (30 mL). After 1.5 hours the reaction mixture was added to a mixture of ice and 1N HCl (149 mL, 149 mmol) and reaction flask rinsed with THF (5 ml) and combined with the aqueous mixture. The resulting mixture was diluted with 10% aq LiCl and the pH was adjusted to 4.00 with 1N NaOH. The mixture was extracted with Et2O, washed with brine, dried over MgSO4, filtered and concentrated. The resulting residue was purified on silica gel column (220 g ISCO) eluting with a gradient from 10% EtOAc/hexane to 30% EtOAc/hexane. The product was collected and concentrated to give (2-amino-3-methylphenyl)(3-fluorophenyl)methanone (7.11 g, 94% yield) as an oil. MS(ES):m/z=230.1 [M+H+]; HPLC: RT=2.820 min Purity=99%. (H2O/MeOH with TFA, CHROMOLITH® ODS S5 4.6×50 mm, gradient=4 min, wavelength=220 nm);

1. customto give a slightly cloudy yellow solution
2. washrinsed with THF (5 ml)
3. additionThe resulting mixture was diluted with 10% aq LiCl
4. extractionThe mixture was extracted with Et2O
5. washwashed with brine
6. dry with materialdried over MgSO4
7. filtrationfiltered
8. concentrationconcentrated
9. customThe resulting residue was purified on silica gel column (220 g ISCO)
10. washeluting with a gradient from 10% EtOAc/hexane to 30% EtOAc/hexane
11. customThe product was collected
12. concentrationconcentrated

ORD record

ord-81b1db3dadab4ed3981764246fb86246

Source dataset

uspto-grants-2015_09

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US09133139B2