Diethyl Ether → 3-Phthalimido-3-(4-butoxy-3-methoxyphenyl)propionic acid

HRID 1421311Notes

Reaction equation

HRID 1421311 reaction equation
[NH2:1][CH:2]([C:7]1[CH:12]=[CH:11][C:10]([O:13][CH2:14][CH2:15][CH2:16][CH3:17])=[C:9]([O:18][CH3:19])[CH:8]=1)[CH2:3][C:4]([OH:6])=[O:5].C(=O)([O-])[O-].[Na+].[Na+].C(N1[C:35](=[O:36])[C:34]2=[CH:37][CH:38]=[CH:39][CH:40]=[C:33]2[C:32]1=[O:41])(OCC)=O.CCOCC>O.C(#N)C>[C:32]1(=[O:41])[N:1]([CH:2]([C:7]2[CH:12]=[CH:11][C:10]([O:13][CH2:14][CH2:15][CH2:16][CH3:17])=[C:9]([O:18][CH3:19])[CH:8]=2)[CH2:3][C:4]([OH:6])=[O:5])[C:35](=[O:36])[C:34]2=[CH:37][CH:38]=[CH:39][CH:40]=[C:33]12

Participants

7

Reactant 4

HCID 3283Diethyl EtherHCID 10340Sodium CarbonateHCID 31187N-CarbethoxyphthalimideHCID 16641995HCID 16641995, compound

Product 1

HCID 98870583-Phthalimido-3-(4-butoxy-3-methoxyphenyl)propionic acidYield 51.5%

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 6342AcetonitrileSolvent

Procedure

To a stirred solution of 3-amino-3-(4-butoxy-3-methoxyphenyl)propionic acid (1.31 g, 4.98 mmol) and sodium carbonate (0.554 g, 5.23 mmol) in a mixture of 100 mL of water and 100 mL of acetonitrile (mixture was warmed gently to dissolve solid, small amount of brown solid did not dissolve removed by filtration) was added N-carbethoxyphthalimide (1.09 g, 4.98 mmol). The mixture was stirred for 1 hour, then partially concentrated in vacuo to remove the acetonitrile. The pH was adjusted to 0-1 with 4 N Hydrochloric acid. An oil formed, 3 mL of ether was added and the mixture stirred overnight. The oil did not solidify and was extracted in methylene chloride. The organic layer was dried (sodium sulfate) and concentrated to a yellow oil which was purified by flash chromatography (silica gel, 5/95 methanol/methylene chloride) to afford 1.02 g of 3-phthalimido-3-(4-butoxy-3-methoxyphenyl)propionic acid containing an unidentified impurity as a yellow oil which slowly crystallized: 1H NMR (DMSO-d6)δ 7.95-7.8 (m, 4H, Ar), 7.03 (s, 1H), 6.9 (m, 2H), 5.61 (dd, 1H, J=9, 6.7 Hz), 3.91 (t, 2H, J=6.4 Hz), 3.74 (s, 3H), 3.47 (dd, 1H, J=16.5, 6.7 Hz), 3.27 (dd, 1H, J=16.5, 6.7 Hz), 1.75-1.55 (m, 2H) 1.5-1.3 (m, 2H), 0.91 (t, 3H, J=7.3 Hz); 13C NMR (DMSO-d6)δ 171.8, 167.7, 148.8, 147.8, 134.6, 131.3, 131.1, 123.2, 119.3, 112.9, 111.4, 67.8, 55.5, 50.1, 30.8, 18.7, 13.6.

Workup

  1. temperaturewas warmed gently
  2. dissolutionto dissolve solid, small amount of brown solid
  3. dissolutiondid not dissolve
  4. customremoved by filtration)
  5. concentrationpartially concentrated in vacuo
  6. customto remove the acetonitrile
  7. customAn oil formed
  8. stirringthe mixture stirred overnight
  9. extractionwas extracted in methylene chloride
  10. dry with materialThe organic layer was dried (sodium sulfate)
  11. concentrationconcentrated to a yellow oil which
  12. customwas purified by flash chromatography (silica gel, 5/95 methanol/methylene chloride)

Sources & evidence

ORD record
ord-66fd38a086fe49c4bffecec75caf9560
Source dataset
uspto-grants-2000_06
Patent number
US06075041

Reaction notes

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