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A 250 ml round bottom flask charged with 6-fluoro-3,4-dihydro-2H-benzo[b][1,4]oxazine (5.00 g, 32.6 mmol) was dried under high vacuum and placed under nitrogen prior to the addition of THF (131 ml). The solution was cooled in an ice water bath for 10 mins prior to the addition of sodium hydride (60% in mineral oil) (1.436 g, 35.9 mmol), added carefully in two portions 5 mins apart. The resulting suspension was stirred for 15 min at 0° C. then 90 min at room temp yielding a brownish suspension. To the suspension was added 2-fluoro-5-(trifluoromethyl)benzonitrile (6.79 g, 35.9 mmol) at room temperature. The mixture was stirred at 60° C. overnight affording about 75% conversion according to LC-MS. The dark solution was cooled in an ice water bath and carefully added to a stirred flask of water/ice/NH4Cl which was extracted with EtOAc (2×). The combined organics were dried with Na2SO4, filtered, and dried under reduced pressure. The crude residue was purified with a 120 g ISCO gold column (load column loaded with crude brown oil directly with DCM rinsing) ramping EtOAc in heptane (0-25%, then isocratic at 25%) providing product cleanly (3.65 g, yellow solid) as well as a large portion which coeluted with starting amine and other minor impurities. The mixture was dried under reduced pressure and passed through a 25 g SCX-2 column, then a second 25 g SCX-2 column since after the first wash some dark materials eluted through. DCM was used as the eluent providing 2-(6-fluoro-2H-benzo[b][1,4]oxazin-4(3 H)-yl)-5-(trifluoromethyl)benzonitrile as a tan solid (3.0 g) (6.65 g total, 63%). 1H NMR (400 MHz, CHLOROFORM-d) δ ppm 3.84-3.91 (m, 2 H) 4.26-4.31 (m, 2 H) 6.53 (dd, J=9.93, 2.89 Hz, 1 H) 6.64 (ddd, J=9.00, 7.82, 2.93 Hz, 1 H) 6.90 (dd, J=8.95, 5.33 Hz, 1 H) 7.55 (d, J=8.71 Hz, 1 H) 7.76 (ddd, J=8.71, 2.25, 0.59 Hz, 1H) 7.95 (dd, J=1.57, 0.68 Hz, 1 H). m/z (ESI) 323.1 (M+H)+.

1. customwas dried under high vacuum
2. additionto the addition of THF (131 ml)
3. temperatureThe solution was cooled in an ice water bath for 10 mins
4. additionadded carefully in two portions 5 mins apart
5. custom90 min at room temp yielding a brownish suspension
6. stirringThe mixture was stirred at 60° C. overnight
7. customaffording about 75% conversion
8. temperatureThe dark solution was cooled in an ice water bath
9. extractionwas extracted with EtOAc (2×)
10. dry with materialThe combined organics were dried with Na2SO4
11. filtrationfiltered
12. customdried under reduced pressure
13. customThe crude residue was purified with a 120 g ISCO gold column (load column
14. customisocratic at 25%) providing product cleanly (3.65 g, yellow solid) as well as a large portion which
15. customThe mixture was dried under reduced pressure
16. washa second 25 g SCX-2 column since after the first wash some dark materials
17. washeluted through