Water → HCID 59263305, compound

Temperature

25 °C

NaHMDS (148 mmol; 27.2 g) was charged to a 1000 ml round-bottomed flask (4 necks, thermometer, pressure-equalising dropping funnel, stopper, nitrogen inlet, magnetically stirred, oven dried, nitrogen purged), followed by DMF (300 ml). The mixture was stirred for 5 minutes then 1-methoxy-2-propanol (1.50 equiv; 148 mmol; 14.3 ml; 13.4 g) was added dropwise over a 10-minute period. The reaction temperature increased to 25° C. The mixture was cooled using a cold-water bath to 23° C., then 3-bromo-5-fluorobenzonitrile (1.00 equiv; 99.0 mmol; 20.0 g) in DMF (90 ml) was added over a 5 minutes period (cold water bath still present). The mixture warmed to 27° C. during addition, turning from yellow to brown. A line wash of DMF (10 ml) was added. The mixture was stirred at ambient temperature for 30 minutes, then quenched by addition of HCl solution (2M, aqueous, 200 ml), the dark brown reaction mixture turning pale yellow. The mixture was poured into water (400 ml) and extracted with EtOAc (3×400 ml). The combined organic extracts were washed with water (3×400 ml) and dried over MgSO4, filtered and the solvent removed in vacuo affording 3-bromo-5-(2-methoxy-1-methylethoxy)benzonitrile as an orange oil (25.38 g, 95%). 1H NMR (400 MHz, CDCl3) δ: 7.32 (s, 1H), 7.26 (s, 1H), 7.11 (s, 1H), 4.58-4.55 (m, 1H), 3.59-3.48 (m, 2H), 3.41 (s, 3H), 1.33-1.31 (d, 3H).

1. customoven dried
2. customnitrogen purged),
3. stirringThe mixture was stirred for 5 minutes
4. temperatureThe mixture was cooled
5. customto 23° C.
6. temperatureThe mixture warmed to 27° C. during addition
7. washA line wash of DMF (10 ml)
8. additionwas added
9. stirringThe mixture was stirred at ambient temperature for 30 minutes
10. customquenched by addition of HCl solution (2M, aqueous, 200 ml)
11. additionThe mixture was poured into water (400 ml)
12. extractionextracted with EtOAc (3×400 ml)
13. washThe combined organic extracts were washed with water (3×400 ml)
14. dry with materialdried over MgSO4
15. filtrationfiltered
16. customthe solvent removed in vacuo

ORD record

ord-12a6113886be475bbf0f480568e08f69

Source dataset

uspto-grants-2010_04

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US07700640B2