Sodium hydride → HCID 57893792, compound

Temperature

80 °C

Combine 1-methyl-piperidin-4-ol (5.97 g, 51.81 mmol) and N,N-dimethylformamide (100 mL) and treat, in portions, the resulting solution with 95% sodium hydride (1.31 g, 51.81 mmol) and stir. After 1 hr., add 1-bromo-3,5-difluoro-benzene (10.0 g, 51.81 mmol), stir and heat to 80° C. After 2 hr., cool to ambient temperature, partition between water (100 mL) and ethyl acetate (100 mL), separate and wash the water layer with ethyl acetate (100 mL). Combine the ethyl acetate layers and wash with water (5×75 mL). Wash the organic layer with aqueous NaCl solution (75 mL), dry over sodium sulfate, filter and concentrate to an oil. Purify the residue by silica gel flash chromatography eluting with 10% (2M NH3/methanol)/methylene dichloride to obtain of the title compound (10.61 g, 71%). Mass spectrum (electrospray): m/z=288 (M+1−1), 290 (M+1+1); 1H NMR (CDCl3): 6.85 (s, 1H), 6.8 (m, 1H), 6.55 (m, 1H), 4.3 (m, 1H), 2.6 (m, 2H), 2.3 (m, 5H), 2.0 (m, 2H), 1.8 (m, 2H).

1. waitAfter 2 hr
2. temperature, cool to ambient temperature
3. custompartition between water (100 mL) and ethyl acetate (100 mL)
4. customseparate
5. washwash the water layer with ethyl acetate (100 mL)
6. washCombine the ethyl acetate layers and wash with water (5×75 mL)
7. washWash the organic layer with aqueous NaCl solution (75 mL)
8. dry with materialdry over sodium sulfate
9. filtrationfilter
10. concentrationconcentrate to an oil
11. customPurify the residue by silica gel flash chromatography
12. washeluting with 10% (2M NH3/methanol)/methylene dichloride

ORD record

ord-362f717abf1842e1abadb98acf562b3c

Source dataset

uspto-grants-2009_10

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US07608629B2