1-Bromo-3-fluorobenzene → HCID 57893715, compound

HRID 1821992Notes

Reaction equation

HRID 1821992 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 450974411-Piperidinecarboxylicacid,4-hydroxy-2-methyl-,1,1-dimethylethylester,(2S,4R)-(9CI)

Product 1

HCID 57893715HCID 57893715, compoundYield 46%

Reagents, catalysts & solvents 1

HCID 13387N-methyl-2-pyrrolidoneSolvent

Conditions

Temperature
100 °C

Procedure

Dissolve 4-hydroxy-trans-2-methyl-piperidine-1-carboxylic acid tert-butyl ester isomer 1 (preparation 2, 3.03 g, 14.07 mmol) in 1-methyl-2-pyrrolidinone (50 mL), treat with 95% sodium hydride (0.33 g, 12.93 mmol), stir and beat at 70° C. After 1 hr., add 1-bromo-3-fluoro-benzene (1.73 mL, 15.5 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 the residue by silica gel flash chromatography eluting with 4:1 hexanes:ethyl acetate to obtain of the title compound (2.42 g, 46%). 1H NMR (CDCl3): 7.1 (m, 3H), 6.8 (m, 1H), 4.55 (m, 1H), 4.5 (m, 1H), 4.1 (m, 1H), 2.95 (m, 1H), 2.1 (m, 1H), 1.95 (m, 1H), 1.7 (m, 1H), 1.5 (m, 1H), 1.45 (s, 9H), 1.2 (d, 3H).

Workup

  1. dissolutionDissolve
  2. customat 70° C
  3. stirringstir
  4. waitAfter 16 hr
  5. temperature, cool to ambient temperature
  6. customquench with water (100 mL)
  7. extractionExtract with 4:1 hexane
  8. washwash with aqueous NaCl solution (75 mL)
  9. dry with materialdry over sodium sulfate
  10. filtrationfilter
  11. concentrationconcentrate
  12. customPurify the residue by silica gel flash chromatography
  13. washeluting with 4:1 hexanes

Sources & evidence

ORD record
ord-d694c2ccbfe04f5db5b8dc16d338c51e
Source dataset
uspto-grants-2009_10
Patent number
US07608629B2

Reaction notes

Loading…