1-Bromo-3-fluorobenzene → HCID 57893757, compound

Temperature

50 °C

Dissolve 1-methyl-piperidin-4-ol (10.06 g, 87.34 mmol) in DMF (30 mL) and add to a stirred suspension of sodium hydride (5.24 g, 131.01 mmol) in DMF (155 mL). After the addition is complete, heat at 50° C. After 45 min., add a solution of 1-bromo-3-fluoro-benzene (12.2 mL, 109.18 mmol) in DMF (15 mL) and stir and heat at 65° C. After 18 hr., cool to ambient temperature, quench with water (5 mL), remove the DMF under reduced pressure, wash with water (50 mL) and extract with ethyl acetate/hexanes (2/1 mixture, 2×35 mL). Combine the organic layers, dry over magnesium sulfate, filter under reduced vacuum and concentrate to dryness. Purify by flash chromatography using dichloromethane/ammonia (2.0M in methanol) 20/1 as the eluent to give of the title compound (15.4 g, 65%). Mass spectrum (ion spray): m/z=270.0 (M+1); 1H NMR (CDCl3): 7.12 (t, J=8.3 Hz, 1H), 7.07-7.04 (m, 2H), 6.83 (bd, J=8.3 Hz, 1H), 4.35-4.26 (bm, 1H), 2.73-2.64 (bm, 2H), 2.37-2.28 (bm, 5H), 2.05-1.96 (bm, 2H), 1.89-1.79 (bm, 2H).

1. additionAfter the addition
2. temperatureheat at 65° C
3. waitAfter 18 hr
4. temperature, cool to ambient temperature
5. customquench with water (5 mL)
6. customremove the DMF under reduced pressure
7. washwash with water (50 mL)
8. extractionextract with ethyl acetate/hexanes (2/1 mixture, 2×35 mL)
9. dry with materialCombine the organic layers, dry over magnesium sulfate
10. filtrationfilter under reduced vacuum
11. concentrationconcentrate to dryness
12. customPurify by flash chromatography

ORD record

ord-6d914d278b5041a59ba5882d16d1098f

Source dataset

uspto-grants-2009_10

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US07608629B2