Dimethylformamide → Ethyl alpha-(4-carbomethoxy-2-n-propyl-phenoxy)-3,4-methylenedioxylphenylacetate

HRID 964462Notes

Reaction equation

HRID 964462 reaction equation
[OH:1][C:2]1[CH:11]=[CH:10][C:5]([C:6]([O:8][CH3:9])=[O:7])=[CH:4][C:3]=1[CH2:12][CH2:13][CH3:14].C(=O)([O-])[O-].[Cs+].[Cs+].Br[CH:22]([C:28]1[CH:33]=[CH:32][C:31]2OC[O:36][C:30]=2[CH:29]=1)[C:23]([O:25][CH2:26][CH3:27])=[O:24].CN([CH:40]=[O:41])C>>[C:6]([C:5]1[CH:10]=[CH:11][C:2]([O:1][CH:22]([C:28]2[CH:29]=[C:30]([OH:36])[C:31]3[CH2:33][C:32]=3[C:40]=2[OH:41])[C:23]([O:25][CH2:26][CH3:27])=[O:24])=[C:3]([CH2:12][CH2:13][CH3:14])[CH:4]=1)([O:8][CH3:9])=[O:7]

Participants

5

Reactant 4

HCID 6228Dimethylformamide2×HCID 10796Cesium carbonateHCID 11805593Methyl 4-hydroxy-3-propylbenzoateHCID 15383768Ethyl alpha-bromo-3,4-methylenedioxyphenylacetate

Product 1

HCID 131720722Ethyl alpha-(4-carbomethoxy-2-n-propyl-phenoxy)-3,4-methylenedioxylphenylacetate

Procedure

To a 2 L three necked 24/40 round bottom flask equipped with a mechanical stirrer, a nitrogen inlet and a dropping funnel was first added a solution of 36.0 g (0.185 mol) of methyl 4-hydroxy-3-n-propylbenzoate dissolved in 700 mL of anhydrous DMF followed by 66.4 g (0.204 mol) of cesium carbonate. The flask was purged with nitrogen and the reaction mixture was stirred at room temperature for 2 hours. A solution of 58.5 g (0.204 mol) of ethyl α-bromo-3,4-methylenedioxyphenylacetate dissolved in 100 mL of DMF was then added via an addition funnel over a 15 minute period. The reaction mixture was stirred an additional 1 hour at room temperature then quenched by addition to 5 L of a 5% aqueous citric acid solution. The organic product was extracted into diethylether (2×4 L), the organic layers were separated, washed with saturated aqueous NaCl, dried (MgSO4), filtered, and evaporated. The residue was applied to a silica gel (2 kg; 70-230 mesh) column equilibrated in 10% CH2 Cl2 -hexane. The column was then eluted successively with 12 L of 10% CH2Cl2 -hexane, 12 L of 5% EtOAc-hexane, 4 L of 7.5% EtOAc-hexane, 12 L of 10% EtOAc-hexane, and finally 8 L of 20% EtOAc-hexane. Combination of the purified fractions and evaporation in vacuo afforded 76.3 g (74.2 theoretical) of the title compound as a pale yellow oil which was used without further purification in the next step.

Workup

  1. customequipped with a mechanical stirrer, a nitrogen inlet and a dropping funnel
  2. customThe flask was purged with nitrogen
  3. additionwas then added via an addition funnel over a 15 minute period
  4. stirringThe reaction mixture was stirred an additional 1 hour at room temperature
  5. customthen quenched by addition to 5 L of a 5% aqueous citric acid solution
  6. extractionThe organic product was extracted into diethylether (2×4 L)
  7. customthe organic layers were separated
  8. washwashed with saturated aqueous NaCl
  9. dry with materialdried (MgSO4)
  10. filtrationfiltered
  11. customevaporated
  12. washThe column was then eluted successively with 12 L of 10% CH2Cl2 -hexane, 12 L of 5% EtOAc-hexane, 4 L of 7.5% EtOAc-hexane, 12 L of 10% EtOAc-hexane, and finally 8 L of 20% EtOAc-hexane
  13. customCombination of the purified fractions and evaporation in vacuo

Sources & evidence

ORD record
ord-af787f1f143445639396a57677ae282e
Source dataset
uspto-grants-1998_06
Patent number
US05767310

Reaction notes

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