Cesium carbonate → HCID 59263319, compound

Temperature

120 °C

3,5-Difluorophenol (2.00 equiv; 51.8 mmol; 6.74 g) was charged to a 100 ml round-bottomed flask (3 necks, 2 stoppers, air condenser with argon inlet, magnetically stirred, oven dried) followed by NMP (471 mmol; 45.3 ml; 46.7 g) and cesium carbonate (51.8 mmol; 16.9 g). The mixture was sparged with argon for 10 minutes then cuprous monochloride (6.48 mmol; 641 mg), 2,2,6,6-tetramethyl-3,5-heptanedione, (1.30 mmol; 271 μl; 239 mg) and 3-bromo-5-(2-methoxy-1-methylethoxy)benzonitrile (1.00 equiv; 25.9 mmol; 7.00 g) were charged sequentially. The mixture was sparged with argon for 5 minutes then heated to 120° C. and stirred for 24 hours. The reaction mixture was cooled and partitioned between HCl solution (1M, aqueous, 200 ml) and MTBE (200 ml). The layers were separated and the organic portion washed with NaOH solution (1M, aq, 200 ml), water (200 ml) and brine (200 ml). The resultant organic solution was dried over MgSO4, filtered and the solvent removed in vacuo affording a brown oil. This material was purified by flash column chromatography affording 3-(3,5-difluorophenoxy)-5-(2-methoxy-1-methylethoxy)benzonitrile as a pale yellow oil (5.17 g, 63%). 1H NMR (400 MHz, CDCl3) δ: 7.01 (s, 1H), 6.86 (m, 2H), 6.62 (m, 1H), 6.53 (m, 2H), 4.54 (m, 1H), 3.53 (m, 2H), 3.39 (s, 3H), 1.32 (d, 3H).

1. customoven dried)
2. customThe mixture was sparged with argon for 10 minutes
3. customThe mixture was sparged with argon for 5 minutes
4. stirringstirred for 24 hours
5. temperatureThe reaction mixture was cooled
6. custompartitioned between HCl solution (1M, aqueous, 200 ml) and MTBE (200 ml)
7. customThe layers were separated
8. washthe organic portion washed with NaOH solution (1M, aq, 200 ml), water (200 ml) and brine (200 ml)
9. dry with materialThe resultant organic solution was dried over MgSO4
10. filtrationfiltered
11. customthe solvent removed in vacuo
12. customaffording a brown oil
13. customThis material was purified by flash column chromatography

ORD record

ord-d1e7c52c418a4de081c7217e2f3ad801

Source dataset

uspto-grants-2010_04

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US07700640B2