Potassium Carbonate → 3-(4-propoxyphenyl)propanoic acid

HRID 1453033Notes

Reaction equation

HRID 1453033 reaction equation
O[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][C:3]=1[CH2:8][CH2:9][C:10]([O:12]C)=[O:11].I[CH2:15][CH2:16][CH3:17].C([O-])([O-])=[O:19].[K+].[K+]>CN(C=O)C>[CH2:15]([O:19][C:6]1[CH:7]=[CH:2][C:3]([CH2:8][CH2:9][C:10]([OH:12])=[O:11])=[CH:4][CH:5]=1)[CH2:16][CH3:17]

Participants

5

Reactant 3

HCID 11430Potassium CarbonateHCID 336431-IodopropaneHCID 2794569Methyl 3-(2-hydroxyphenyl)propionate

Product 1

HCID 22559353-(4-propoxyphenyl)propanoic acidYield 98.1%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Conditions

Temperature
60 °C

Procedure

To a solution of methyl 3-(hydroxyphenyl)propionate (15 g, 83.24 mmol) and iodopropane (12.14 mL, 124.5 mmol) in DMF (80 mL) was added K2CO3 (34 g, 249.7 mmol). The resultant slurry was stirred vigorously and heated to 60° C. under argon for 12 h. DMF was evaporated and residue partitioned between EtOAC and 1N HCl. The organic layer was washed with H2O, and brine then dried over Na2SO4. The solvent was removed in vacuo and the residue was purified by flash column chromatography (10% EtOAc in hexanes) to provide the desired product (17 g, 98%) as a clear oil. The resultat oil was dissolved in THF (150 mL), and 2M NaOH (68 mL) was added. The reaction was stirred overnight at room temperature. THF was evaporated and residue acidified with concentrated HCl and extracted 3 times with EtOAC (100 mL). The organic layer was washed with H2O, dried over Na2SO4 and concentrated to a white solid which was recrystalized from hexanes to provide the desired product (14.06 g 82%). 1H NMR (CDCl3) δ: 1.04 (t, J=7.2, 3H), 1.76-1.85 (m, 2H), 2.64 (t, J=8.1, 2H), 2.90 (t, J=8.1, 2H), 3.89 (t, J=6.6, 2H), 6.82 (d, J=8.6, 2H), 7.10 (d, J=8.6, 2H).

Workup

  1. customDMF was evaporated
  2. customresidue partitioned between EtOAC and 1N HCl
  3. washThe organic layer was washed with H2O, and brine
  4. dry with materialthen dried over Na2SO4
  5. customThe solvent was removed in vacuo
  6. customthe residue was purified by flash column chromatography (10% EtOAc in hexanes)

Sources & evidence

ORD record
ord-d0b731f4cb3c4b1099bd9e43f974cc6a
Source dataset
uspto-grants-2009_01
Patent number
US07473790B2

Reaction notes

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