Ammonia → HCID 18787107, compound

Temperature

0 °C

Sodium hydride (60% dispersion in mineral oil, 0.90 g, 25.2 mmol) was added to a stirred, cooled (0° C.) solution of N-(3-bromo-4-methoxyphenyl)acetamide (4.58 g. 18.8 mmol) in dimethylformamide (60 ml). The mixture was stirred at 0° C. for 30 minutes, then propargyl bromide (80% solution in toluene, 2.51 ml, 25.2 mmol) was added. The mixture was stirred at room temperature for 30 minutes, then water (150 ml) was added. The mixture was extracted with ethyl acetate (3×150 ml) and the combined organic fractions were washed water (4×150 ml) and brine (150 ml), dried (MgSO4) and evaporated under reduced pressure. The residue was dissolved in acetic acid (15 ml) and mercury (II) acetate (0.90 g, 2.8 mmol) and ammonium acetate (14.47 g, 188 mmol) were added. The mixture was heated under reflux for 4 hours, cooled and poured into water (150 ml). The pH was adjusted to 10.0 with saturated aqueous ammonia and the mixture was extracted with ethyl acetate (3×150 ml). The combined organic fractions were washed with brine (150 ml), dried (MgSO4) and evaporated under reduced pressure. The residue was purified by flash column chromatography on silica gel, eluting with CH2Cl2 /MeOH/NH3 (Aq.) (95:5:0.5) and the residue was recrystallized from ethyl acetate (30 ml)/hexane (60 ml). The solid was collected and dried in vacuo to give the title compound as a cream-coloured solid (4.98 g, 94%), 1H NMR (360 MHz, CDCl3) δ 7.48 (1H, d, J=2.6 Hz), 7.19 (1H, dd, J=8.7, 2.6 Hz), 6.95 (1H, d, J=8.7 Hz), 6.66 (1H, s), 3.95 (3H, s), 2.30 (3H, s), and 2.22 (3H, s).

1. stirringThe mixture was stirred at room temperature for 30 minutes
2. extractionThe mixture was extracted with ethyl acetate (3×150 ml)
3. washthe combined organic fractions were washed water (4×150 ml) and brine (150 ml)
4. dry with materialdried (MgSO4)
5. customevaporated under reduced pressure
6. dissolutionThe residue was dissolved in acetic acid (15 ml)
7. temperatureThe mixture was heated
8. temperatureunder reflux for 4 hours
9. temperaturecooled
10. extractionthe mixture was extracted with ethyl acetate (3×150 ml)
11. washThe combined organic fractions were washed with brine (150 ml)
12. dry with materialdried (MgSO4)
13. customevaporated under reduced pressure
14. customThe residue was purified by flash column chromatography on silica gel
15. washeluting with CH2Cl2 /MeOH/NH3 (Aq.) (95:5:0.5)
16. customthe residue was recrystallized from ethyl acetate (30 ml)/hexane (60 ml)
17. customThe solid was collected
18. customdried in vacuo

ORD record

ord-186c869d775b4340b89cce41a4db0a13

Source dataset

uspto-grants-2000_05

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US06060469