Hydrochloric Acid → 1-Ethoxy-3-(3'-ethoxy-4'-methoxyphenyl)-3-phthalimidopropane

HRID 1941251Notes

Reaction equation

HRID 1941251 reaction equation
[CH2:1]([O:3][C:4]1[CH:5]=[C:6]([CH:12]([N:16]2[C:20](=[O:21])[C:19]3=[CH:22][CH:23]=[CH:24][CH:25]=[C:18]3[C:17]2=[O:26])[CH2:13][CH2:14][OH:15])[CH:7]=[CH:8][C:9]=1[O:10][CH3:11])[CH3:2].[CH2:27](Br)[CH3:28].[H-].[Na+].Cl>[I-].C([N+](CCCC)(CCCC)CCCC)CCC.C1COCC1.[NH4+].[Cl-]>[CH2:27]([O:15][CH2:14][CH2:13][CH:12]([C:6]1[CH:7]=[CH:8][C:9]([O:10][CH3:11])=[C:4]([O:3][CH2:1][CH3:2])[CH:5]=1)[N:16]1[C:20](=[O:21])[C:19]2=[CH:22][CH:23]=[CH:24][CH:25]=[C:18]2[C:17]1=[O:26])[CH3:28]

Participants

8

Reactant 4

HCID 313Hydrochloric AcidHCID 6332Ethyl BromideHCID 24758Sodium hydrideHCID 214605203-(3'-Ethoxy-4'-methoxyphenyl)-3-phthalimido-1-propanol

Product 1

HCID 214605291-Ethoxy-3-(3'-ethoxy-4'-methoxyphenyl)-3-phthalimidopropaneYield 74%

Reagents, catalysts & solvents 3

HCID 25517Ammonium ChlorideCatalystHCID 67553Tetrabutylammonium IodideCatalystHCID 8028TetrahydrofuranSolvent

Procedure

To a stirred solution of 3-(3'-ethoxy-4'-methoxyphenyl)-3-phthalimido-1-propanol (1 gram, 2.82 mmol), ethyl bromide (0.42 mL, 5.63 mmol), and tetrabutyl ammonium iodide (200 mg, 0.54 mmol) in THF (10 mL) at room temperature, was added NaH (270 mg, 60%, 6.75 mmol). The mixture was stirred at room temperature for 45 minutes, and then was heated to reflux for 4 h. To the mixture was added a few drops of NH4Cl, then HCl (1N, 25 mL). The organic layer was separated. The aqueous layer was extracted with ethyl acetate (3×25 mL). The combined organic layers were washed with brine (25 mL), and dried over magnesium sulfate. Removal of solvent and chromatography (silica gel 100 grams, 1:5 EtOAc:hexane) gave 1-ethoxy-3-(3'-ethoxy-4'-methoxyphenyl)-3-phthalimidopropane as an oil, (800 mg, 74% yield): 1H NMR (CDCl3)δ1.06 (t, J=7Hz, 3H, CH3), 1.46 (t, J=7 Hz, 3H, CH3), 2.46-2.58 (m, 1H, CHH), 2.75-2.95 (m, 1H, CHH), 3.37 (q, J=7 Hz, 2H, CH2), 3.44 (q, J=7 Hz, 2H, CH2), 3.85 (s, 3H, CH3), 4.12 (q, J=7 Hz, 2H, CH2), 5.49 (dd, J=6.4, 9.5 Hz, 1H, NCH), 6.81 (d, J=8.2 Hz, 1H, Ar), 7.10-7.48 (m, 2H, Ar), 7.68-7.72 (m, 2H, Ar), 7.77-7.83 (m, 2H, Ar); 13C NMR (CDCl3)δ14.73, 14.98, 31.31, 52.24, 55.89, 64.30, 66.33, 67.73, 111.11, 112.99, 120.61, 123.11, 132.00, 132.09, 133.80, 148.11, 148.84, 168.44; Anal Calcd for C22H25NO5 : C, 68.91; H, 6.57; N, 3.65. Found: C, 68.77; H, 6.47; N, 3.57.

Workup

  1. temperaturewas heated
  2. temperatureto reflux for 4 h
  3. customThe organic layer was separated
  4. extractionThe aqueous layer was extracted with ethyl acetate (3×25 mL)
  5. washThe combined organic layers were washed with brine (25 mL)
  6. dry with materialdried over magnesium sulfate
  7. customRemoval of solvent and chromatography (silica gel 100 grams, 1:5 EtOAc:hexane)

Sources & evidence

ORD record
ord-7a91aeec5456493e9470e3895f677c03
Source dataset
uspto-grants-1997_12
Patent number
US05703098

Reaction notes

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