Formic Acid → 2-(S)-ethoxy-3-(4-{2-[4-(formylamino)phenyl]ethoxy}-phenyl)propanoic acid ethyl ester

HRID 987318Notes

Reaction equation

HRID 987318 reaction equation
[CH:1](O)=[O:2].N1C=CN=C1.C(N(CC)CC)C.C(Cl)(=O)C(Cl)=O.Cl.[CH2:23]([O:25][C:26](=[O:48])[C@@H:27]([O:45][CH2:46][CH3:47])[CH2:28][C:29]1[CH:34]=[CH:33][C:32]([O:35][CH2:36][CH2:37][C:38]2[CH:43]=[CH:42][C:41]([NH2:44])=[CH:40][CH:39]=2)=[CH:31][CH:30]=1)[CH3:24]>ClCCl.C(OCC)(=O)C.CCCCCCC.O>[CH2:23]([O:25][C:26](=[O:48])[C@@H:27]([O:45][CH2:46][CH3:47])[CH2:28][C:29]1[CH:34]=[CH:33][C:32]([O:35][CH2:36][CH2:37][C:38]2[CH:39]=[CH:40][C:41]([NH:44][CH:1]=[O:2])=[CH:42][CH:43]=2)=[CH:31][CH:30]=1)[CH3:24]

Participants

9

Reactant 5

HCID 284Formic AcidHCID 795ImidazoleHCID 8471Triethylamine2×HCID 65578Oxalyl chlorideHCID 86595066HCID 86595066, compound

Product 1

HCID 544253382-(S)-ethoxy-3-(4-{2-[4-(formylamino)phenyl]ethoxy}-phenyl)propanoic acid ethyl esterYield 47%

Reagents, catalysts & solvents 3

HCID 962WaterSolventHCID 6344DichloromethaneSolvent3×HCID 21899848Ethylacetate heptaneSolvent

Procedure

Formic acid (0.0585 g, 1.27 mmole) was dissolved in dichloromethane (2 ml). Imidazole (0.0874 g; 1.27 mmole) was added into the solution, followed by addition of triethylamine (0.353 ml, 2.54 mmole). The mixture was stirred for a little while and then oxalyl chloride (0.161 g; 1.27 mmole) in dichloromethane (2 ml) was added slowly. The resulting mixture was stirred for 30 minutes. A mixture of 3-{4-[2-(4-aminophenyl)ethoxy]phenyl}-(S)-2-ethoxypropanoic acid ethyl ester hydro chloride (described in Example 41b) (0.5 g, 1.27 mmole) and triethylamine (0.176 ml; 1.27 mmole) in dichloromethane (3 ml) was added into the reaction mixture. The reaction mixture was stirred at room temperature overnight. Water was added and the phases were separated. The organic phase was washed with water, dried with magnesium sulfate and the solvent was evaporated. Chromatography of the residue on silica gel (isolute, SI) using heptane, then ethyl acetate/heptane (5%), followed by ethyl acetate/heptane (10%) and then ethyl acetate/heptane (25%) as eluants gave 0.230 g (47% yield) of 2-(S)-ethoxy-3-(4-{2-[4-(formylamino)phenyl]ethoxy}-phenyl)propanoic acid ethyl ester.

Workup

  1. stirringThe resulting mixture was stirred for 30 minutes
  2. additionwas added into the reaction mixture
  3. stirringThe reaction mixture was stirred at room temperature overnight
  4. customthe phases were separated
  5. washThe organic phase was washed with water
  6. dry with materialdried with magnesium sulfate
  7. customthe solvent was evaporated

Sources & evidence

ORD record
ord-c96180d15b9b4d29a98d3050ad77cdd1
Source dataset
uspto-grants-2003_10
Patent number
US06630600B1

Reaction notes

Loading…