Triethylamine → cis 2-(3,4,5-Trimethoxyphenyl)-5-(3-phthalimidyl propoxy) tetrahydrofuran

HRID 482005Notes

Reaction equation

HRID 482005 reaction equation
[CH3:1][O:2][C:3]1[CH:4]=[C:5]([CH:13]2[CH2:17][CH2:16][CH:15]([OH:18])[O:14]2)[CH:6]=[C:7]([O:11][CH3:12])[C:8]=1[O:9][CH3:10].C(N(CC)CC)C.FC(F)(F)C(OC(=O)C(F)(F)F)=O.[C:39]1(=[O:53])[N:43]([CH2:44][CH2:45][CH2:46]O)[C:42](=[O:48])[C:41]2=[CH:49][CH:50]=[CH:51][CH:52]=[C:40]12>ClCCl>[CH3:12][O:11][C:7]1[CH:6]=[C:5]([C@H:13]2[CH2:17][CH2:16][C@@H:15]([O:18][CH2:46][CH2:45][CH2:44][N:43]3[C:39](=[O:53])[C:40]4=[CH:52][CH:51]=[CH:50][CH:49]=[C:41]4[C:42]3=[O:48])[O:14]2)[CH:4]=[C:3]([O:2][CH3:1])[C:8]=1[O:9][CH3:10]

Participants

6

Reactant 4

HCID 8471TriethylamineHCID 9845Trifluoroacetic anhydrideHCID 701602-(3-Hydroxypropyl)isoindoline-1,3-dioneHCID 190650382-(3,4,5-Trimethoxyphenyl)-5-hydroxy-tetrahydrofuran

Product 1

HCID 86751456cis 2-(3,4,5-Trimethoxyphenyl)-5-(3-phthalimidyl propoxy) tetrahydrofuranYield 46%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Conditions

Temperature
0 °C

Procedure

Compound 105 (1.14 g, 4.49 mmol) was dissolved in 4 mL dichloromethane. Triethylamine (681.4 mg, 6.73 mmol) was added to this solution. The reaction mixture was cooled with an ice bath and trifluoroacetic anhydride (1.41 g, 6.73 mmol) was added in a dropwise manner. The reaction mixture was stirred at 0° C. for 30 minutes and then 3-phthalimidylpropanol (106) (2.4 g, 13.26 mmol) was added. The reaction mixture was warmed to room temperature and stirred at room temperature for 2 hours. The reaction was quenched with saturated aqueous NaHCO3 solution and extracted with ethyl acetate. The organic layer was washed with water and saturated NaCl solution, dried over MgSO4, filtered and evaporated in vacuo to an oil which was purified by column chromatography (silica, 2:1 hexane/ethyl acetate) (107: 522 mg (trans); 108: 271 mg (cis); 1:1 mixture of 107 and 108: 110 mg; total yield 46%). 1H NMR (CDCl3): 107: 1.70(m,1H); 1.82(m,1H); 2.00(m,2H); 2.02(m,1H); 2.28(m,1H); 3.46(m,1H); 3.83(s,3H); 3.84(m,3H); 3.88(s,6H); 4.99(t,1H); 5.30(dd,1H); 6.56(s,2H); 7.72(m,2H); 7.85(m,2H). 108: 1.95(m,3H); 2.00(m,2H); 2.20(m,1H); 3.51(m,1H); 3.83(s,3H); 3.85(m,2H); 3.88(s,6H); 3.92(m,1H); 4.90(m,1H); 5.16(dd,1H); 6.60(s,2H); 7.72(m,2H); 7.84(m,2H).

Workup

  1. temperatureThe reaction mixture was cooled with an ice bath
  2. temperatureThe reaction mixture was warmed to room temperature
  3. stirringstirred at room temperature for 2 hours
  4. customThe reaction was quenched with saturated aqueous NaHCO3 solution
  5. extractionextracted with ethyl acetate
  6. washThe organic layer was washed with water and saturated NaCl solution
  7. dry with materialdried over MgSO4
  8. filtrationfiltered
  9. customevaporated in vacuo to an oil which
  10. customwas purified by column chromatography (silica, 2:1 hexane/ethyl acetate) (107: 522 mg (trans); 108: 271 mg (cis); 1:1 mixture of 107 and 108: 110 mg; total yield 46%)

Sources & evidence

ORD record
ord-968385d8480547b39eebc4337cf04b9f
Source dataset
uspto-grants-1998_08
Patent number
US05792776

Reaction notes

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