Tetrahydrofuran → N-[2-(4-methoxy-3-methylphenyl)ethyl]-1-(1,2,3,4-tetrahydronaphth-1-yl)cyclopropanecarboxamide

HRID 2393115Notes

Reaction equation

HRID 2393115 reaction equation
Cl.[CH3:2][O:3][C:4]1[CH:9]=[CH:8][C:7]([CH2:10][CH2:11][NH2:12])=[CH:6][C:5]=1[CH3:13].C(N([CH2:19][CH3:20])CC)C.[OH-].[Na+].[O:23]1[CH2:27][CH2:26][CH2:25][CH2:24]1>>[CH3:2][O:3][C:4]1[CH:9]=[CH:8][C:7]([CH2:10][CH2:11][NH:12][C:27]([C:26]2([CH:8]3[C:19]4[C:20](=[CH:9][CH:4]=[CH:5][CH:6]=4)[CH2:11][CH2:10][CH2:7]3)[CH2:24][CH2:25]2)=[O:23])=[CH:6][C:5]=1[CH3:13]

Participants

5

Reactant 4

HCID 8028Tetrahydrofuran3×HCID 8471Triethylamine2×HCID 14798Sodium HydroxideHCID 189756582-(4-Methoxy-3-methyl-phenyl)-ethylamine Hydrochloride

Product 1

HCID 18975707N-[2-(4-methoxy-3-methylphenyl)ethyl]-1-(1,2,3,4-tetrahydronaphth-1-yl)cyclopropanecarboxamide

Procedure

A solution of 1,1-carbonyldiimidazole (3.2 g) in tetrahydrofuran (50 ml) was added slowly to a solution of the product from the previous reaction (4.3 g) in tetrahydrofuran (50 ml) and the mixture stirred for 18 hours. 2-(4-Methoxy-3-methylphenyl)ethylamine hydrochloride (4.0 g) then triethylamine (2.8 ml) were added and the mixture stirred for 18 hours. As the reaction had not gone to completion a solution of further starting amine (3.09 g) and triethylamine (2.1 ml) in tetrahydrofuran (20 ml) was added and stirring continued for three days. As the reaction remained incomplete, dilute aqueous sodium hydroxide solution (200 ml) was added and stirring continued for 18 hours. The organic layer was separated and the aqueous layer extracted with ethyl acetate (4×150 ml). The combined organics were washed with brine then dried over magnesium sulphate and the solvent removed in vacuo. The residue was washed well with petroleum ether (bp 60°-80° C.) to give crude N-[2-(4-methoxy-3-methylphenyl)ethyl]-1(1,2,3,4-tetrahydronaphth-1-yl)cyclopropanecarboxamide (7.0 g) as a brown gum which was used without further purification.

Workup

  1. stirringthe mixture stirred for 18 hours
  2. additionwas added
  3. stirringstirring
  4. waitcontinued for three days
  5. stirringstirring
  6. waitcontinued for 18 hours
  7. customThe organic layer was separated
  8. extractionthe aqueous layer extracted with ethyl acetate (4×150 ml)
  9. washThe combined organics were washed with brine
  10. dry with materialthen dried over magnesium sulphate
  11. customthe solvent removed in vacuo
  12. washThe residue was washed well with petroleum ether (bp 60°-80° C.)

Sources & evidence

ORD record
ord-38ed507a2c3c473c932880b92d4548c6
Source dataset
uspto-grants-1998_09
Patent number
US05804586

Reaction notes

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