1-Bromo-3-fluorobenzene → HCID 57893670, compound

HRID 1821993Notes

Reaction equation

HRID 1821993 reaction equation
[CH2:1]([N:8]1[CH2:13][CH2:12][C@H:11]([OH:14])[C@H:10]([CH3:15])[CH2:9]1)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.[H-].[Na+].[Br:18][C:19]1[CH:24]=[CH:23][CH:22]=[C:21](F)[CH:20]=1>CN(C)C=O>[CH2:1]([N:8]1[CH2:13][CH2:12][C@H:11]([O:14][C:21]2[CH:22]=[CH:23][CH:24]=[C:19]([Br:18])[CH:20]=2)[C@H:10]([CH3:15])[CH2:9]1)[C:2]1[CH:3]=[CH:4][CH:5]=[CH:6][CH:7]=1

Participants

5

Reactant 3

HCID 140821-Bromo-3-fluorobenzeneHCID 24758Sodium hydrideHCID 57893755cis-1-Benzyl-3-methylpiperidin-4-ol

Product 1

HCID 57893670HCID 57893670, compound

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Conditions

Temperature
80 °C

Procedure

Dissolve 1-benzyl-cis-3-methyl-piperidin-4-ol (preparation 6, 3.84 g, 18.73 mmol) in dry N,N-dimethylformamide (100 mL), treat with 60% sodium hydride (1.05 g, 26.22 mmol), heat and stir at 80° C. After 1 hr., add-1-bromo-3-fluoro-benzene (2.51 mL, 22.45 mmol), stir and heat at 110° C. After 16 hr., cool to ambient temperature. Partition between water (100 mL) and ethyl acetate (100 mL), wash the aqueous layer with ethyl acetate (2×100 mL), combine the organic layers, wash with water (5×100 mL) and aqueous NaCl solution (100 mL). Dry the organic layer over sodium sulfate, filter and concentrate. Purify the residue by silica gel flash chromatography eluting with 2% (2M NH3/methanol)/methylene dichloride to obtain the title compound as a mixture of enantiomers (1.69 g, 24%). 1H NMR (CDCl3): 7.3 (m, 5H), 7.1 (m, 3H), 6.8 (m, 1H), 4.3 (m, 1H), 3.5 (d, 2H), 2.5 (m, 2H), 2.4 (m, 2H), 2.0 (m, 2H), 1.8 (m, 1H), 1.0 (d, 3H).

Workup

  1. temperatureheat
  2. stirringstir
  3. temperatureheat at 110° C
  4. waitAfter 16 hr
  5. temperature, cool to ambient temperature
  6. customPartition between water (100 mL) and ethyl acetate (100 mL)
  7. washwash the aqueous layer with ethyl acetate (2×100 mL)
  8. washwash with water (5×100 mL) and aqueous NaCl solution (100 mL)
  9. dry with materialDry the organic layer over sodium sulfate
  10. filtrationfilter
  11. concentrationconcentrate
  12. customPurify the residue by silica gel flash chromatography
  13. washeluting with 2% (2M NH3/methanol)/methylene dichloride

Sources & evidence

ORD record
ord-f100d98cfb044d30bd580fbf503b7211
Source dataset
uspto-grants-2009_10
Patent number
US07608629B2

Reaction notes

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