Iodine → 4-[3-(Methylsulfanyl)phenyl]-1-propylpiperidin-4-ol

HRID 2280366Notes

Reaction equation

HRID 2280366 reaction equation
Br[C:2]1[CH:3]=[C:4]([S:8][CH3:9])[CH:5]=[CH:6][CH:7]=1.[Mg].II.[CH2:13]([N:16]1[CH2:21][CH2:20][C:19](=[O:22])[CH2:18][CH2:17]1)[CH2:14][CH3:15]>C(OCC)C>[CH3:9][S:8][C:4]1[CH:3]=[C:2]([C:19]2([OH:22])[CH2:20][CH2:21][N:16]([CH2:13][CH2:14][CH3:15])[CH2:17][CH2:18]2)[CH:7]=[CH:6][CH:5]=1

Participants

6

Reactant 4

HCID 807IodineHCID 900061-Propyl-4-piperidoneHCID 27356273-Bromothioanisole3×HCID 5462224Magnesium

Product 1

HCID 299817804-[3-(Methylsulfanyl)phenyl]-1-propylpiperidin-4-ol

Reagents, catalysts & solvents 1

HCID 3283Diethyl EtherSolvent5×

Procedure

3-Bromothioanisole (960 mg, 4.73 mmol) was dissolved in 10 mL of diethyl ether dried on Na. 1-Propyl-4-piperidone was dissolved in 8 mL of dry diethyl ether. Approximately 10% of the solution of 3-bromothioanisole in dry diethyl ether was added to magnesium (344 mg, 14.15 mmol) and a few iodine crystals in a dried 250 mL three-necked flask in a nitrogen atmosphere. When the brown mixture turned colourless, the remaining solution of 3-bromothioanisole in dry diethyl ether was added drop wise, while refluxing on a hot water bath in a nitrogen atmosphere. When all the solution was added, the reaction mixture was left to reflux for twenty minutes. Then, 10 mL of dry diethyl ether was added because of evaporation. It was left to reflux for 30 minutes. The reaction mixture turned yellow and then green. Gas forming was noticed even before refluxing. Then the reaction mixture was left to cool to room temperature. The solution of 1-propyl-4-piperidone in dry diethyl ether was added drop wise to the reaction mixture. The reaction mixture then consisted of a dark oil, white precipitation and some clear solution. The reaction mixture was worked up with saturated NH4Cl solution (30 mL). The organic layer was separated. The aqueous layer was extracted twice with diethyl ether. The organic layers were collected and washed with brine and dried on MgSO4 during the night. The solution was filtered and the solvent evaporated in vacuo on a rotavapor. No further purification. Yield: 460 mg (56%). IR (KBr): 3113, 2956, 2917, 2828, 2772, 2365, 1583, 1444, 1375, 1148, 1104, 1044, 780, 696 cm−1; 1H-NMR (CDCl3, 300 MHz): δ 7.280 (d), 7.159 (m), 2.820 (d), 2.484 (s), 2.433 (t), 2.195 (t), 1.761 (d), 1.588 (t), 0.924 (t) ppm; 13C-NMR (CDCl3, 300 MHz): δ 127.291, 123.521, 121.359, 119.865, 69.826, 59.311, 47.947, 36.864, 18.573, 14.310, 10.524 ppm; GCMS (EI): m/z 265 (M+), 236 (M−29), 218, 206, 118; GC (100-320° C., 15° C./min): 7.6 min.

Workup

  1. customdried on Na
  2. dissolution1-Propyl-4-piperidone was dissolved in 8 mL of dry diethyl ether
  3. temperaturewhile refluxing on a hot water bath in a nitrogen atmosphere
  4. additionWhen all the solution was added
  5. waitthe reaction mixture was left
  6. temperatureto reflux for twenty minutes
  7. waitIt was left
  8. temperatureto reflux for 30 minutes
  9. customGas forming
  10. temperaturebefore refluxing
  11. waitThen the reaction mixture was left
  12. customThe reaction mixture then consisted of a dark oil, white precipitation
  13. customThe organic layer was separated
  14. extractionThe aqueous layer was extracted twice with diethyl ether
  15. customThe organic layers were collected
  16. washwashed with brine
  17. customdried on MgSO4 during the night
  18. filtrationThe solution was filtered
  19. customthe solvent evaporated in vacuo on a rotavapor
  20. customNo further purification
  21. customGC (100-320° C., 15° C./min)
  22. custom7.6 min.

Sources & evidence

ORD record
ord-e7706e1d978a46cea46f1dbc647ce3a4
Source dataset
uspto-grants-2015_09
Patent number
US09139525B2

Reaction notes

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