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To a flask charged with 5-fluoro-3,4-dihydro-2H-benzo[b][1,4]oxazine (Combi-Blocks) (0.321 g, 2.096 mmol) was added THF (8.38 ml). The solution was cooled in an ice water bath prior to the addition of sodium hydride (60% in mineral oil) (0.092 g, 2.306 mmol). The resulting suspension was stirred for 30 mins at 0° C., the 30 mins at room temp. The resulting pale yellow suspension was cooled in an ice water bath prior to the addition of 2-fluoro-5-(trifluoromethyl)benzonitrile (Matrix Scientific) (0.436 g, 2.306 mmol). The mixture was stirred for 5 mins at 0° C., the 1 hr at room temperature when LC-MS indicated all starting material present. The tannish suspension was heated to reflux overnight providing a brown solution with about 80% conversion to product according to LC-MS. The mixture was cooled to room temperature and carefully added to ice water 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 25 g column (25 m spherical silica gel, Interchim) ramping EtOAc in heptane (0-35%, with 10% DCM throughout) providing product which had partially coeluted with starting amine. The material obtained was filtered through a 5 g SCX-2 column washing with MeOH. The MeOH wash contained product, obtained as an off-white solid 2-(5-fluoro-2H-benzo[b][1,4]oxazin-4(3H)-yl)-5-(trifluoromethyl)benzonitrile (0.450 g, 1.396 mmol, 66.6% yield). 1H NMR (400 MHz, CHLOROFORM-d) δ ppm 3.91-3.97 (m, 2 H) 4.22 (br. s., 2 H) 6.68 (ddd, J=10.86, 8.22, 1.37 Hz, 1 H) 6.82 (dt, J=8.41, 1.37 Hz, 1 H) 7.00 (td, J=8.31, 5.97 Hz, 1 H) 7.14 (dd, J=8.71, 2.25 Hz, 1 H) 7.67 (ddd, J=8.73, 2.23, 0.59 Hz, 1 H) 7.90 (dd, J=1.57, 0.59 Hz, 1 H). m/z (ESI) 323.3 (M+H)+.

1. temperatureThe solution was cooled in an ice water bath
2. customthe 30 mins
3. customat room temp
4. temperatureThe resulting pale yellow suspension was cooled in an ice water bath
5. stirringThe mixture was stirred for 5 mins at 0° C.
6. customthe 1 hr
7. customat room temperature
8. temperatureThe tannish suspension was heated
9. temperatureto reflux overnight
10. customproviding a brown solution with about 80% conversion to product
11. temperatureThe mixture was cooled to room temperature
12. extractionwas extracted with EtOAc (2×)
13. dry with materialThe combined organics were dried with Na2SO4
14. filtrationfiltered
15. customdried under reduced pressure
16. customThe crude residue was purified with a 25 g column (25 m spherical silica gel, Interchim)
17. customproviding product which
18. customThe material obtained
19. filtrationwas filtered through a 5 g SCX-2 column
20. washwashing with MeOH
21. washThe MeOH wash