4-Bromotoluene → HCID 14698737, compound

HRID 1709843Notes

Reaction equation

HRID 1709843 reaction equation
Br[C:2]1[CH:7]=[CH:6][C:5]([CH3:8])=[CH:4][CH:3]=1.[Mg].C(O[C:13]([CH:15]1[CH2:20][CH2:19][N:18]([CH2:21][C:22]2[CH:27]=[CH:26][CH:25]=[CH:24][CH:23]=2)[CH2:17][CH2:16]1)=[O:14])C.[Cl-].[NH4+]>O1CCCC1>[CH3:8][C:5]1[CH:6]=[CH:7][C:2]([C:13]([C:2]2[CH:7]=[CH:6][C:5]([CH3:8])=[CH:4][CH:3]=2)([CH:15]2[CH2:16][CH2:17][N:18]([CH2:21][C:22]3[CH:23]=[CH:24][CH:25]=[CH:26][CH:27]=3)[CH2:19][CH2:20]2)[OH:14])=[CH:3][CH:4]=1

Participants

6

Reactant 4

HCID 78054-BromotolueneHCID 25517Ammonium ChlorideHCID 90423Ethyl 1-benzylpiperidine-4-carboxylateHCID 5462224Magnesium

Product 1

HCID 14698737HCID 14698737, compoundYield 95.4%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent3×

Procedure

A Grignard solution was prepared by the addition of 102.6 g (0.6 mole) of 4-bromotoluene in 500 ml of dry tetrahydrofuran to a mixture of 12.5 g (0.5 mole) of magnesium chips in 250 ml of tetrahydrofuran. After the addition was complete, the mixture was heated at reflux for 1 hr to complete formation. To this Grignard reagent at ambient temperature was added in a stream 42.9 g (0.173 mole) of 1-(phenylmethyl)-4-piperidinecarboxylic acid ethyl ester in 250 ml of dry tetrahydrofuran. The solution was stirred at ambient temperature and then poured into 2.5 liters of a saturated ammonium chloride solution. The layers were separated and the aqueous layer was extracted twice with 375 ml portions of methylene chloride. The combined organic layers were washed successively with 500 ml of water, 750 ml of a 3% sodium hydroxide solution, 250 ml of water and 250 ml of brine. The organic layer was dried over sodium sulfate and concentrated under pressure to give a gum as residue. The gum gradually cyrstallized. The solid was triturated with petroleum ether (30°-60° C.), collected by filtration and dried to yield 63.6 g (95%) of title compound as a white solid. An analytical sample was recrystallized from 2-propanol, mp 115°-117° C.

Workup

  1. additionAfter the addition
  2. temperaturethe mixture was heated
  3. temperatureat reflux for 1 hr
  4. customThe layers were separated
  5. extractionthe aqueous layer was extracted twice with 375 ml portions of methylene chloride
  6. washThe combined organic layers were washed successively with 500 ml of water, 750 ml of a 3% sodium hydroxide solution, 250 ml of water and 250 ml of brine
  7. dry with materialThe organic layer was dried over sodium sulfate
  8. concentrationconcentrated under pressure
  9. customto give a gum as residue
  10. customThe solid was triturated with petroleum ether (30°-60° C.)
  11. filtrationcollected by filtration
  12. customdried

Sources & evidence

ORD record
ord-630db1a6fd4f419393d932a0e5921b75
Source dataset
uspto-grants-1990_08
Patent number
US04950674

Reaction notes

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