Iodine → 1-Benzyl-3-(3-methoxyphenyl)piperidine

HRID 2280369Notes

Reaction equation

HRID 2280369 reaction equation
Br[C:2]1[CH:3]=[C:4]([O:8][CH3:9])[CH:5]=[CH:6][CH:7]=1.[Mg].II.[CH2:13]([N:20]1[CH2:25][CH2:24][CH2:23][C:22](=O)[CH2:21]1)[C:14]1[CH:19]=[CH:18][CH:17]=[CH:16][CH:15]=1.[NH4+].[Cl-]>C(OCC)C.C(OC(=O)C)C>[CH3:9][O:8][C:4]1[CH:3]=[C:2]([CH:22]2[CH2:23][CH2:24][CH2:25][N:20]([CH2:13][C:14]3[CH:19]=[CH:18][CH:17]=[CH:16][CH:15]=3)[CH2:21]2)[CH:7]=[CH:6][CH:5]=1

Participants

8

Reactant 5

HCID 807IodineHCID 169713-Bromoanisole3×HCID 25517Ammonium ChlorideHCID 966503-Piperidinone, 1-(phenylmethyl)-HCID 5462224Magnesium

Product 1

HCID 129379391-Benzyl-3-(3-methoxyphenyl)piperidine

Reagents, catalysts & solvents 2

HCID 3283Diethyl EtherSolvent4×HCID 8857Ethyl AcetateSolvent

Procedure

3-Bromoanisole (14.824 g, 79.26 mmol) was dissolved in 160 mL of diethyl ether dried on Na. Approximately 10% of the solution of 3-bromoanisole in dry diethyl ether was added to magnesium (1.927 g, 79.27 mmol) and a few iodine crystals in a dried 500 mL three-necked flask in a nitrogen atmosphere while stirring. Almost instantly, H2 gas was visible. The brown mixture turned colourless. The remaining solution of 3-bromoanisole in dry diethyl ether was added drop wise. Gas forming was noticed during and after this. After 1 h, a lot of white precipitate was noticed. 1-Benzyl-3-piperidone (5.000 g, 26.42 mmol) was dissolved in 120 mL of dry diethyl ether and added to the reaction mixture drop wise at 30° C. The fine white/yellow precipitate turned more coarse and brownish. Stirring was continued at room temperature for 1 h. Then the suspension was poured in a Erlenmeyer flask and 150 mL of saturated NH4Cl solution was added. About 50 mL of ethylacetate was added to wash out the three-necked flask. The suspension was stirred for 5 min. The organic layer was separated and the aqueous layer was extracted three times with diethyl ether. The organic layers were collected, washed with brine and dried on NaSO4 overnight. The solution was filtered and the solvent evaporated. The residue (about 12.000 g) was extracted with ether once, the solvent evaporated. Yield: 7.6 g (32%). GCMS (EI): m/z 297 (M+), 206 (M−91), 177, 147, 134; GC (100-320° C., 15° C./min): 9.1 min.

Workup

  1. customdried on Na
  2. customGas forming
  3. additionadded to the reaction mixture drop wise at 30° C
  4. waitwas continued at room temperature for 1 h
  5. additionwas added
  6. washto wash out the three-necked flask
  7. stirringThe suspension was stirred for 5 min
  8. customThe organic layer was separated
  9. extractionthe aqueous layer was extracted three times with diethyl ether
  10. customThe organic layers were collected
  11. washwashed with brine
  12. customdried on NaSO4 overnight
  13. filtrationThe solution was filtered
  14. customthe solvent evaporated
  15. extractionThe residue (about 12.000 g) was extracted with ether once
  16. customthe solvent evaporated
  17. customGC (100-320° C., 15° C./min)
  18. custom9.1 min.

Sources & evidence

ORD record
ord-99477ffcd6e24bf8a1f75667e71eb03e
Source dataset
uspto-grants-2015_09
Patent number
US09139525B2

Reaction notes

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