Benzene → 3-[4-(2-Aminoethoxy)phenyl]-2-ethoxypropionic acid ethyl ester

HRID 1060859Notes

Reaction equation

HRID 1060859 reaction equation
Br[CH2:2][CH2:3][O:4][C:5]1[CH:10]=[CH:9][C:8]([CH2:11][CH:12]([O:18][CH2:19][CH3:20])[C:13]([O:15][CH2:16][CH3:17])=[O:14])=[CH:7][CH:6]=1.C1(=O)[NH:25]C(=O)C2=CC=CC=C12.[K].CN(C)C=O.C1C=CC=CC=1>O>[NH2:25][CH2:2][CH2:3][O:4][C:5]1[CH:10]=[CH:9][C:8]([CH2:11][CH:12]([O:18][CH2:19][CH3:20])[C:13]([O:15][CH2:16][CH3:17])=[O:14])=[CH:7][CH:6]=1

Participants

6

Reactant 4

HCID 241BenzeneHCID 6228DimethylformamideHCID 11002461Ethyl 2-ethoxy-3-[4-(2-bromoethoxy)-phenyl]propanoateHCID 24194345Phthalimide potassium salt

Product 1

HCID 108589313-[4-(2-Aminoethoxy)phenyl]-2-ethoxypropionic acid ethyl esterYield 96.9%

Reagents, catalysts & solvents 1

HCID 962WaterSolvent

Conditions

Temperature
100 °C

Procedure

A mixture of ethyl 3-(4-(2-bromethoxy)phenyl)-2-ethoxypropanoate (3.05 g, 8.8 mmol), potassium phtalimide (2.0 g, 10.8 mmol) and dimethylformamide (20 ml) was heated to 100° C. for 16 h, benzene (200 ml) and water (200 ml) were added and the phases were separated. The organic phase was dried and the solvent evaporated in vacuo. The residue was dissolved in ethanol (60 mL), hydrazine hydrate (1.3 ml) was added and the mixture was refluxed for 2 h, filtered and the solvent evaporated to give 2.4 g (96%) of ethyl 3-(4-(2-aminoethoxy) phenyl)-2-ethoxypropanoate as an oil. Hydrogen oxalate hemihydrate was prepared for characterization by neutralization with oxalic acid in acetone. M.p. 146-148° C. A mixture of dibenzo[b,f9-1,4-thiazepin-11(10H)-thione (2.20 g, 9 mmol; prepared as described in Coll.Czech.Chem.Commun. 48, 1465 (1983), 3-(4-(2-aminoethoxy)phenyl)-2-ethoxypropanoic acid ethyl ester (2.60 g, 8.9 mmol) and 3-methyl-1-butanol (70 ml) was stirred and heated at 150° C. for 16 h. The solvent was evaporated in vacuo, dichloromethane (50 ml) and water (50 ml) were added, the mixture was filtered and the phases were separated. The organic phase was dried (MgSO4) and the solvent was evaporated in vacuo to give a residue which was purified by column chromatography on silica gel eluting with chloroform. This afforded 0.7 g of the starting thione and then 1.7 g (38%) of the title compound as an oil. 1H NMR (250 MHz, CDCl3) δ7.05-7.50 (m, 9 H), 6.85-6.95 (m, 3 H), 5.15 (bs, 1 H), 4.25 (m, 2 H), 4.16 (q, J=7.2 Hz, 2 H), 3.96 (t+m, 3 H), 3.59 (m, 1 H), 3.34 (m, 1 H), 2.95 (d, J=6.4 Hz, 2 H), 1.22 (t, J=7.2 Hz, 3 H), 1.16 (t, J=7.2 Hz, 3 H).

Workup

  1. customthe phases were separated
  2. customThe organic phase was dried
  3. customthe solvent evaporated in vacuo
  4. dissolutionThe residue was dissolved in ethanol (60 mL)
  5. additionhydrazine hydrate (1.3 ml) was added
  6. temperaturethe mixture was refluxed for 2 h
  7. filtrationfiltered
  8. customthe solvent evaporated

Sources & evidence

ORD record
ord-2d9bfa6f86c54e0bb05f0640e04b5783
Source dataset
uspto-grants-2003_02
Patent number
US06525086B2

Reaction notes

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