Ethanol, 2-methoxy-, sodium salt (1:1) → 7-Ethyl-1-[(2-methoxyethyl)methyl]-3,4-dihydroisoquinoline

HRID 2383063Notes

Reaction equation

HRID 2383063 reaction equation
[CH3:1][O:2][CH2:3][CH2:4][O-].[Na+].Cl.Cl[CH2:9][C:10]1[C:19]2[C:14](=[CH:15][CH:16]=[C:17]([CH2:20][CH3:21])[CH:18]=2)[CH2:13][CH2:12][N:11]=1>COCCO.COC(O)C.C1COCC1>[CH2:20]([C:17]1[CH:18]=[C:19]2[C:14]([CH2:13][CH2:12][N:11]=[C:10]2[CH2:9][CH2:4][CH2:3][O:2][CH3:1])=[CH:15][CH:16]=1)[CH3:21]

Participants

6

Reactant 2

HCID 23673640Ethanol, 2-methoxy-, sodium salt (1:1)HCID 675376241-(Chloromethyl)-7-ethyl-3,4-dihydroisoquinoline hydrochloride

Product 1

HCID 675380887-Ethyl-1-[(2-methoxyethyl)methyl]-3,4-dihydroisoquinoline

Reagents, catalysts & solvents 3

HCID 80192-MethoxyethanolSolventHCID 8028TetrahydrofuranSolventHCID 30156371-MethoxyethanolSolvent

Conditions

Temperature
60 °C

Procedure

Under cooling in an ice bath, a mixture of sodium hydride (suspension of 8 g of sodium hydride in mineral oil (60%) washed with hexane) in THF (10 mL) was added to methoxyethanol (100 mL) under stirring over 20 minutes to produce sodium 2-methoxyethoxide, followed by further stirring for 2 hours. A solution of sodium 2-methoxyethoxide in 2-methoxyethanol (55 mL) was added with stirring to a solution of 1-(chloromethyl)-7-ethyl-3,4-dihydroisoquinoline hydrochloride (8.5 g) in methoxyethanol (50 mL) under cooling in an ice bath, for 5 minutes. The reaction mixture was heated at 60° C., followed by stirring for 3 hours under an argon atmosphere. The reaction mixture was cooled to room temperature and diluted with THF (150 mL), followed by filtration. The filtrate was concentrated under reduced pressure. To the resulting residue was added a saturated aqueous ammonium chloride solution and the residue was extracted with EtOAc. The organic layer was washed with water and a saturated aqueous sodium chloride solution, dried over magnesium sulfate, and concentrated under reduced pressure. The resulting residue was purified by silica gel column chromatography (hexane:EtOAc) to obtain 7-ethyl-1-[(2-methoxyethyl)methyl]-3,4-dihydroisoquinoline (2.13 g).

Workup

  1. temperatureunder cooling in an ice bath, for 5 minutes
  2. stirringby stirring for 3 hours under an argon atmosphere
  3. temperatureThe reaction mixture was cooled to room temperature
  4. filtrationfollowed by filtration
  5. concentrationThe filtrate was concentrated under reduced pressure
  6. additionTo the resulting residue was added a saturated aqueous ammonium chloride solution
  7. extractionthe residue was extracted with EtOAc
  8. washThe organic layer was washed with water
  9. dry with materiala saturated aqueous sodium chloride solution, dried over magnesium sulfate
  10. concentrationconcentrated under reduced pressure
  11. customThe resulting residue was purified by silica gel column chromatography (hexane:EtOAc)

Sources & evidence

ORD record
ord-b928a96c68e449b480c643611952a9c4
Source dataset
uspto-grants-2012_09
Patent number
US08263607B2

Reaction notes

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