Methyl iodide → 3-(3'-Ethoxy-4'-methoxyphenyl)-1-methoxy-3-phthalimidopropane

HRID 1941249Notes

Reaction equation

HRID 1941249 reaction equation
[H-].[Na+].I[CH3:4].[CH2:5]([O:7][C:8]1[CH:9]=[C:10]([CH:16]([N:20]2[C:24](=[O:25])[C:23]3=[CH:26][CH:27]=[CH:28][CH:29]=[C:22]3[C:21]2=[O:30])[CH2:17][CH2:18][OH:19])[CH:11]=[CH:12][C:13]=1[O:14][CH3:15])[CH3:6].[NH4+].[Cl-]>C1COCC1>[CH2:5]([O:7][C:8]1[CH:9]=[C:10]([CH:16]([N:20]2[C:24](=[O:25])[C:23]3=[CH:26][CH:27]=[CH:28][CH:29]=[C:22]3[C:21]2=[O:30])[CH2:17][CH2:18][O:19][CH3:4])[CH:11]=[CH:12][C:13]=1[O:14][CH3:15])[CH3:6]

Participants

6

Reactant 4

HCID 6328Methyl iodideHCID 24758Sodium hydrideHCID 25517Ammonium ChlorideHCID 214605203-(3'-Ethoxy-4'-methoxyphenyl)-3-phthalimido-1-propanol

Product 1

HCID 214605123-(3'-Ethoxy-4'-methoxyphenyl)-1-methoxy-3-phthalimidopropaneYield 41%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

To a stirred mixture of sodium hydride (110 mg, 60%, 2.75 mmol) in THF (8 mL) at room temperature, was added iodomethane (0.54 grams, 3.78 mmol) followed by 3-(3'-ethoxy-4'-methoxyphenyl)-3-phthalimido-1-propanol (850 mg, 2.39 mmol). The mixture was stirred at room temperature for 15 h. To the mixture was added NH4Cl (20 mL, sat). The organic layer was separated. The aqueous layer was extracted with methylene chloride (2×50 mL). The combined organic layers were washed with brine (50 mL) and dried over magnesium sulfate. Removal of solvent and chromatography (silica gel 200 grams, 1:12 EtOAc:CH2Cl2) gave 3-(3'-ethoxy-4'-methoxyphenyl)-1-methoxy-3-phthalimidopropane as an oil (360 mg, 41% yield). The resulting oil solidified after standing at room temperature over weekend: mp, 67.5°-70.0° C.; 1H NMR (CDCl3)δ1.45 (t, J=7 Hz, 3H, CH3), 2.50-2.60 (m, 1H, CHH), 2.71-2.85 (m, 1H, CHH), 3.26 (s, 3H, CH3), 3.39 (t, J=6 Hz, 2H, CH2), 3.84 (s, 3H, CH3), 4.10 (q, J=7 Hz, 2H, CH2), 5.47 (dd, J=7, 9.3 Hz, 1H, NCH), 6.81 (d, J=Hz, 1H, Ar), 7.09-7.16 (m, 2H, Ar), 7.66-7.69 (m, 2H, Ar), 7.76-7.82 (m, 2H, Ar). 13C NMR (CDCl3)δ(APT) 14.67 (CH3), 31.23 (CH2), 51.89 (CH3), 58.63 (CH), 64.25 (CH2), 69.62 (CH2), 111.13 (CH), 112.98 (CH), 120.58 (CH), 123.06 (CH), 131.87 (C), 131.92 (C), 133.78 (CH), 148.09 (C), 148.84 (C), 168.33 (C); Anal Calcd for C21H23NO5 0.05H2O: C, 67.66; H, 6.23; N, 3.75. Found: C, 67.91; H, 6.00; N, 3.71.

Workup

  1. customThe organic layer was separated
  2. extractionThe aqueous layer was extracted with methylene chloride (2×50 mL)
  3. washThe combined organic layers were washed with brine (50 mL)
  4. dry with materialdried over magnesium sulfate
  5. customRemoval of solvent and chromatography (silica gel 200 grams, 1:12 EtOAc:CH2Cl2)

Sources & evidence

ORD record
ord-e7e8c8991e1e4fc4bac6c22ea3682b44
Source dataset
uspto-grants-1997_12
Patent number
US05703098

Reaction notes

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