1-Bromo-3-fluorobenzene → HCID 57893679, compound

HRID 1821990Notes

Reaction equation

HRID 1821990 reaction equation
[C:1]([O:5][C:6]([N:8]1[CH2:13][CH2:12][C@H:11]([OH:14])[CH2:10][C@@H:9]1[CH3:15])=[O:7])([CH3:4])([CH3:3])[CH3:2].[H-].[Na+].[Br:18][C:19]1[CH:24]=[CH:23][CH:22]=[C:21](F)[CH:20]=1>CN1CCCC1=O>[C:1]([O:5][C:6]([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)[CH2:10][C@@H:9]1[CH3:15])=[O:7])([CH3:4])([CH3:2])[CH3:3]

Participants

5

Reactant 3

HCID 140821-Bromo-3-fluorobenzeneHCID 24758Sodium hydrideHCID 450974401-Piperidinecarboxylicacid,4-hydroxy-2-methyl-,1,1-dimethylethylester,(2S,4S)-(9CI)

Product 1

HCID 57893679HCID 57893679, compoundYield 57%

Reagents, catalysts & solvents 1

HCID 13387N-methyl-2-pyrrolidoneSolvent

Conditions

Temperature
70 °C

Procedure

Dissolve 4-hydroxy-cis-2-methyl-piperidine-1-carboxylic acid tert-butyl ester isomer 1 (preparation 2, 2.53 g, 11.75 mmol) in 1-methyl-2-pyrrolidinone (50 mL) and treat with 95% sodium hydride (0.33 g, 12.93 mmol), stir and heat at 70° C. After 1 hr., add 1-bromo-3-fluoro-benzene (1.44 mL, 12.93 mmol), stir and heat at 100° C. After 16 hr., cool to ambient temperature and quench with water (100 mL). Extract with 4:1 hexane:ethyl acetate (2×100 mL). Combine the organic layers and wash with aqueous NaCl solution (75 mL), dry over sodium sulfate, filter and concentrate. Purify residue by silica gel flash chromatography eluting with 4:1 hexanes:ethyl acetate to obtain the title compound (2.47 g, 57%). 1H NMR (CDCl3): 7.15 (m, 1H), 7.05 (m, 2H), 6.8 (dd, 1H), 4.6 (m, 1H), 4.35 (m, 1H), 3.9 (m, 1H), 3.25 (m, 1H), 1.9 (m, 3H), 1.75 (m, 1H), 1.5 (s, 9H), 1.3 (d, 3H).

Workup

  1. dissolutionDissolve
  2. stirringstir
  3. temperatureheat at 100° C
  4. waitAfter 16 hr
  5. temperature, cool to ambient temperature
  6. customquench with water (100 mL)
  7. extractionExtract with 4:1 hexane
  8. washCombine the organic layers and wash with aqueous NaCl solution (75 mL)
  9. dry with materialdry over sodium sulfate
  10. filtrationfilter
  11. concentrationconcentrate
  12. washPurify residue by silica gel flash chromatography eluting with 4:1 hexanes

Sources & evidence

ORD record
ord-16d73f7ee3ea489889dcb822a89958dc
Source dataset
uspto-grants-2009_10
Patent number
US07608629B2

Reaction notes

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