Tetrahydrofuran → HCID 23093676, compound

HRID 1667311Notes

Reaction equation

HRID 1667311 reaction equation
Br[C:2]1[CH:7]=C(C)C(OC)=C(C)[CH:3]=1.[CH3:12]CCCCC.[CH2:18]([Li])[CH2:19][CH2:20][CH3:21].[O:23]=[CH:24][CH2:25][CH:26]1[CH2:31][CH2:30][N:29]([C:32]([O:34][C:35]([CH3:38])([CH3:37])[CH3:36])=[O:33])[CH2:28][CH2:27]1.[O:39]1CCC[CH2:40]1>O>[OH:23][CH:24]([C:18]1[C:2]([CH3:7])=[CH:3][C:21]([O:39][CH3:40])=[CH:20][C:19]=1[CH3:12])[CH2:25][CH:26]1[CH2:27][CH2:28][N:29]([C:32]([O:34][C:35]([CH3:38])([CH3:37])[CH3:36])=[O:33])[CH2:30][CH2:31]1

Participants

7

Reactant 5

HCID 8028Tetrahydrofuran3×HCID 8058HexaneHCID 2786544-Bromo-2,6-dimethylanisoleHCID 10353694tert-Butyl 4-(2-oxoethyl)piperidine-1-carboxylateHCID 178418339Butyllithium

Product 1

HCID 23093676HCID 23093676, compound

Reagents, catalysts & solvents 1

HCID 962WaterSolvent

Conditions

Temperature
-78 °C

Procedure

Under cooling at −78° C., a solution of 1.50 g of 4-bromo-2,6-dimethylanisole in 20 ml of tetrahydrofuran was added to a solution of 1.6M hexane solution of 4.8 ml of n-butyl lithium in 20 ml of tetrahydrofuran. The mixture was stirred for 1 hour. A solution of 1.50 g of tert-butyl 4-(2-oxoethyl)piperidine-1-carboxylate in 20 ml of tetrahydrofuran was added to the mixture. After stirring for 30 minutes, the mixture was stirred at ambient temperature for further 3 hours. The reaction mixture was poured into water, followed by extraction with ethyl acetate. The organic layer was washed with saturated aqueous sodium chloride and then dried over anhydrous sodium sulfate. After filtration, the filtrate was concentrated and the resulting residue was purified by silica gel column chromatography (hexane-ethyl acetate) to give 628 mg of tert-butyl 4-[2-hydroxy-2-(4-methoxy-2,6-dimethylphenyl)ethyl]piperidine-1-carboxylate as an oil. To the oil was added 15 ml of 10% hydrochloric acid and the mixture was heated under reflux for 2 hours. After cooling, the reaction mixture was alkalized with 20% aqueous sodium hydroxide solution, followed by extraction with ethyl acetate. The organic layer was washed with saturated aqueous sodium chloride and then dried over anhydrous magnesium sulfate. The solvent was evaporated under reduced pressure to give 291 mg of tert-butyl 4-[(E)-2-(4-methoxy-2,6-dimethylphenyl)vinyl]piperidine-1-carboxylate.

Workup

  1. stirringAfter stirring for 30 minutes
  2. stirringthe mixture was stirred at ambient temperature for further 3 hours
  3. extractionfollowed by extraction with ethyl acetate
  4. washThe organic layer was washed with saturated aqueous sodium chloride
  5. dry with materialdried over anhydrous sodium sulfate
  6. filtrationAfter filtration
  7. concentrationthe filtrate was concentrated
  8. customthe resulting residue was purified by silica gel column chromatography (hexane-ethyl acetate)

Sources & evidence

ORD record
ord-9e2bb451328b48678a0b53cb04fa87c8
Source dataset
uspto-grants-2011_10
Patent number
US08044206B2

Reaction notes

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