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

HRID 1941252Notes

Reaction equation

HRID 1941252 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)[C:28]1[CH:33]=[CH:32][CH:31]=[CH:30][CH:29]=1.[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])[C:28]1[CH:33]=[CH:32][CH:31]=[CH:30][CH:29]=1

Participants

8

Reactant 4

HCID 313Hydrochloric AcidHCID 7498Benzyl BromideHCID 24758Sodium hydrideHCID 214605203-(3'-Ethoxy-4'-methoxyphenyl)-3-phthalimido-1-propanol

Product 1

HCID 214605261-Benzyloxy-3-(3'-ethoxy-4'-methoxyphenyl)-3-phthalimidopropaneYield 60%

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 (680 mg, 1.92 mmol), benzyl bromide (0.46 mL, 3.86 mmol), and tetrabutyl ammonium iodide (80 mg, 0.21 mmol) in THF (20 mL) at room temperature, was added NaH (240 mg, 60%, 6.0 mmol). The mixture was stirred at room temperature for 15 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-benzyloxy-3-(3'-ethoxy-4'-methoxyphenyl)-3-phthalimidopropane as an oil, (510 mg, 60% yield): 1H NMR (CDCl3)δ1.46 (t, J=6.9 Hz, 3H, CH3), 2.51-2.59 (m, 1H, CHH), 2.86-2.96 (m, 1H, CHH), 3.51 (t, J=5.5 Hz, CH2), 3.85 (s, 3H, CH3), 4.10 (q, J=7 Hz, CH2), 4.43 (s, 2H, PhCH2), 5.54 (dd, J=6.5, 9.5 Hz, 1H, NCH), 6.80 (d, J=8 Hz, 1H, Ar), 7.09-7.27 (m, 7H, Ar), 7.65-7.79 (m, 4H, Ar); 13C NMR (CDCl3)δ14.73, 31.37, 52.12, 55.88, 64.29, 67.31, 73.10, 111.11, 112.95, 120.59, 123.09, 127.42, 127.62, 128.22, 131.92, 132.09, 133.77, 138.09, 148.12, 148.84, 168.42; Anal Calcd for C27H27 NO5 : C, 72.79; H, 6.11; N, 3.14. Found: C, 72.66; H, 6.32; N, 3.16.

Workup

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

Sources & evidence

ORD record
ord-669e5dbdfebe40059b14809b1675a89e
Source dataset
uspto-grants-1997_12
Patent number
US05703098

Reaction notes

Loading…