Hydrochloric Acid → 3-(3'-Cyclopentyloxy-4'-methoxyphenyl)-1-methoxy-3-phthalimidopropane

HRID 1941250Notes

Reaction equation

HRID 1941250 reaction equation
[CH:1]1([O:6][C:7]2[CH:8]=[C:9]([CH:15]([N:19]3[C:23](=[O:24])[C:22]4=[CH:25][CH:26]=[CH:27][CH:28]=[C:21]4[C:20]3=[O:29])[CH2:16][CH2:17][OH:18])[CH:10]=[CH:11][C:12]=2[O:13][CH3:14])[CH2:5][CH2:4][CH2:3][CH2:2]1.[CH3:30]I.[H-].[Na+].Cl>C1COCC1.[NH4+].[Cl-]>[CH:1]1([O:6][C:7]2[CH:8]=[C:9]([CH:15]([N:19]3[C:20](=[O:29])[C:21]4=[CH:28][CH:27]=[CH:26][CH:25]=[C:22]4[C:23]3=[O:24])[CH2:16][CH2:17][O:18][CH3:30])[CH:10]=[CH:11][C:12]=2[O:13][CH3:14])[CH2:2][CH2:3][CH2:4][CH2:5]1

Participants

7

Reactant 4

HCID 313Hydrochloric AcidHCID 6328Methyl iodideHCID 24758Sodium hydrideHCID 214605383-(3'-Cyclopentyloxy-4'-methoxyphenyl)-3-phthalimido-1-propanol

Product 1

HCID 214605183-(3'-Cyclopentyloxy-4'-methoxyphenyl)-1-methoxy-3-phthalimidopropaneYield 63%

Reagents, catalysts & solvents 2

HCID 25517Ammonium ChlorideCatalystHCID 8028TetrahydrofuranSolvent

Procedure

To a solution of 3-(3'-cyclopentyloxy-4'-methoxyphenyl)-3-phthalimido-1-propanol (786 mg, 1.99 mmol) and methyl iodide (0.25 mL, 4.0 mmol) in THF (1 0 mL) at room temperature, was added NaH (160 mg, 60%, 4.0 mmol). The mixture was stirred at room temperature for 1 h, and then was refluxed for 35 minutes. The mixture was allowed to cool to room temperature. To the resulting 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 (3×30 mL). The combined organic layers were washed with brine (25 mL), and dried over Na2SO4. Removal of solvent and chromatography (silica gel 100 grams, 1:5 EtOAc:hexane) gave 3-(3'-cyclopentyloxy-4'-methoxyphenyl)-1-methoxy-3-phthalimidopropane as an oil, (510 mg, 63% yield). The oil solidified upon standing at room temperature to give a white solid: mp, 77.5°-80.0° C.; 1H NMR (CDCl3)δ1.58-1.96 (m, 8H, C5H8), 2.45-2.55 (m, 1H, CHH), 2.70-2.85 (m, 1H, CHH), 3.26 (s, 3H, CH3), 3.39 (t, J=6 Hz, 2H, CH2), 3.81 (s, 3H, CH3), 4.78-4.80 (m, 1H, OCH), 5.46 (dd, J=7, 9.3 Hz, 1H, NCH), 6.79 (d, J=8.3 Hz, 1H, Ar), 7.06-7.10 (m, 1H, Ar), 7.17-7.26 (m, 1H, Ar), 7.67-7.69 (m, 2H, Ar), 7.78-7.82 (m, 2H, Ar); 13C NMR (CDCl3)δ24.08, 31.30, 32.76, 51.94, 56.00, 58.71, 69.71, 80.37, 111.63, 115.09, 120.53, 123.12, 131.92, 131.96, 133.81, 147.53, 149.55, 169.37; Anal Calcd for C24H27NO5 : C, 70.40; H, 6.65; N, 3.42. Found: C, 70.32; H, 6.61; N, 3.31.

Workup

  1. temperaturewas refluxed for 35 minutes
  2. temperatureto cool to room temperature
  3. customThe organic layer was separated
  4. extractionThe aqueous layer was extracted with ethyl acetate (3×30 mL)
  5. washThe combined organic layers were washed with brine (25 mL)
  6. dry with materialdried over Na2SO4
  7. customRemoval of solvent and chromatography (silica gel 100 grams, 1:5 EtOAc:hexane)

Sources & evidence

ORD record
ord-ceb9a4cfb07842f0a99d08adf36ee7e4
Source dataset
uspto-grants-1997_12
Patent number
US05703098

Reaction notes

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