Sodium Carbonate → 3-(3-Cyclopentyloxy-4-methoxyphenyl)-3-phthalimidopropanoic acid

HRID 323720Notes

Reaction equation

HRID 323720 reaction equation
[NH2:1][CH:2]([C:7]1[CH:12]=[CH:11][C:10]([O:13][CH3:14])=[C:9]([O:15][CH:16]2[CH2:20][CH2:19][CH2:18][CH2:17]2)[CH:8]=1)[CH2:3][C:4]([OH:6])=[O:5].C(=O)([O-])[O-].[Na+].[Na+].C(OC(N1[C:36](=[O:37])[C:35]2=[CH:38][CH:39]=[CH:40][CH:41]=[C:34]2[C:33]1=[O:42])=O)C>C(#N)C.O>[CH:16]1([O:15][C:9]2[CH:8]=[C:7]([CH:2]([N:1]3[C:36](=[O:37])[C:35]4=[CH:38][CH:39]=[CH:40][CH:41]=[C:34]4[C:33]3=[O:42])[CH2:3][C:4]([OH:6])=[O:5])[CH:12]=[CH:11][C:10]=2[O:13][CH3:14])[CH2:17][CH2:18][CH2:19][CH2:20]1

Participants

6

Reactant 3

HCID 10340Sodium CarbonateHCID 31187N-CarbethoxyphthalimideHCID 154354833-Amino-3-(3-cyclopentyloxy-4-methoxyphenyl)propanoic acid

Product 1

HCID 98016133-(3-Cyclopentyloxy-4-methoxyphenyl)-3-phthalimidopropanoic acidYield 68%

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 6342AcetonitrileSolvent

Procedure

A mixture of 3-amino-3-(3-cyclopentyloxy-4-methoxyphenyl)propanoic acid (3.00 g, 10.8 mmol) and sodium carbonate (1.20 g, 11.3 mmol) in acetonitrile (30 mL) and water (30 mL) under nitrogen was stirred at room temperature for 15 minutes. To the resulting solution was added N-ethoxycarbonyl phthalimide (2.36 g, 10.8 mmol). The resulting mixture was stirred at room temperature for 18 hours. Most of solvent was removed in vacuo. To the solution was added hydrochloric acid (6N) until the pH of solution <1 to give a suspension and stirring was continued for 1 hour. The suspension was filtered, the solid was washed with water (2×10 mL), and then was dried in a vacuum oven overnight (60° C., <1 torr) to afford 3-(3-cyclopentyloxy-4-methoxyphenyl)-3-phthalimidopropanoic acid as a white solid (3.0 g, 68% yield): mp, 168.0-169.0° C.; 1H NMR (DMSO-d6) δ1.55-1.88 (m, 8H, C5H8), 3.27 (dd, J=6.9, 16.5 Hz, 1H, CHH), 3.51 (dd, J=8.9, 16.5 Hz, 1H, CHH), 3.71 (s, 3H, CH3), 4.71-4.75 (m, 1H, CH), 5.61 (dd, J=6.9, 8.8 Hz, 1H, NCH), 6.87-6.95 (m, 2H, Ar), 7.03 (br s, 1H, Ar), 7.81-7.91 (m, 4H, Ar), 12.4 (br s, 1H, OH); 13C NMR (DMSO-d6) δ23.51, 32.14, 32.17, 36.07, 50.08, 55.52, 79.57, 112.15, 113.97, 119.39, 123.17, 131.09, 131.19, 134.66, 146.77, 149.16, 167.67, 171.72; Anal Calcd for C23H23NO6: C, 67.47; H, 5.66; N, 3.42. Found: C, 67.21; H, 5.46; N, 3.45.

Workup

  1. stirringThe resulting mixture was stirred at room temperature for 18 hours
  2. customMost of solvent was removed in vacuo
  3. additionTo the solution was added hydrochloric acid (6N) until the pH of solution <1
  4. customto give a suspension
  5. stirringstirring
  6. waitwas continued for 1 hour
  7. filtrationThe suspension was filtered
  8. washthe solid was washed with water (2×10 mL)
  9. customwas dried in a vacuum oven overnight (60° C., <1 torr)

Sources & evidence

ORD record
ord-0092cfc95615493f97e6a3113c542326
Source dataset
uspto-grants-2001_04
Patent number
US06214857B1

Reaction notes

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