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To a stirred solution of 1-(6-fluoropyridin-3-yl)ethanol (2.30 g, 16.3 mmol) and Et3N (4.52 mL, 32.6 mmol) in DCM (50 mL) in 500 mL round-bottomed flask, methanesulfonyl chloride (Aldrich, 1.30 mL, 16.8 mmol) was added dropwise at 0° C. The mixture was stirred at 0° C. for 30 min. Water (50 mL) was added and the layers were separated. The aqueous phase was extracted with DCM (2×30 mL). The combined organic phases were dried over sodium sulfate, filtered and concentrated in vacuo to afford cloudy viscous pale yellow oil. To this intermediate, DCM (40 mL), Et3N (9 mL) and morpholine (5.68 mL, 65.2 mmol) were added and the mixture was stirred at room temperature overnight. THF (5 mL) was added and the stirring was resumed. After overnight stirring, water (60 mL) was added and the layers were separated. The aqueous phase was extracted with EtOAc (2×60 mL). The combined organic phases were dried over sodium sulfate, filtered and concentrated in vacuo. The crude product was purified by silica gel column chromatography (100 g, eluent: iPrOH in CHCl3 0% to 5%) to give 4-(1-(6-fluoropyridin-3-yl)ethyl)morpholine (2.92 g, 85% yield) as a pale yellow oil. 1H NMR (400 MHz, CHLOROFORM-d) δ ppm 8.12 (s, 1H) 7.79 (td, J=8.12, 2.35 Hz, 1H) 6.90 (dd, J=8.41, 2.93 Hz, 1H) 3.68 (t, J=4.60 Hz, 4H) 3.36-3.44 (m, 1H) 2.44-2.56 (m, 2H) 2.30-2.40 (m, 2H) 1.35 (d, J=6.65 Hz, 3H). m/z (ESI, positive ion): 211.1 (M+H)+.

1. customthe layers were separated
2. extractionThe aqueous phase was extracted with DCM (2×30 mL)
3. dry with materialThe combined organic phases were dried over sodium sulfate
4. filtrationfiltered
5. concentrationconcentrated in vacuo
6. customto afford cloudy viscous pale yellow oil
7. stirringthe mixture was stirred at room temperature overnight
8. stirringAfter overnight stirring
9. customthe layers were separated
10. extractionThe aqueous phase was extracted with EtOAc (2×60 mL)
11. dry with materialThe combined organic phases were dried over sodium sulfate
12. filtrationfiltered
13. concentrationconcentrated in vacuo
14. customThe crude product was purified by silica gel column chromatography (100 g, eluent: iPrOH in CHCl3 0% to 5%)