Hydrochloric Acid → 3-(4-{2-[3-(2,4-Difluoro-phenyl)-1-heptyl-ureido]-ethyl}-phenyl)-2-ethoxy-propionic acid methyl ester

HRID 47793Notes

Reaction equation

HRID 47793 reaction equation
Cl.[CH3:2][O:3][C:4](=[O:26])[CH:5]([O:23][CH2:24][CH3:25])[CH2:6][C:7]1[CH:12]=[CH:11][CH:10]=[C:9](CCNCCCCCCC)[CH:8]=1.[F:27][C:28]1[CH:33]=[C:32]([F:34])[CH:31]=[CH:30][C:29]=1[N:35]=[C:36]=[O:37].C([N:41]([CH2:45][CH3:46])[CH:42]([CH3:44])C)(C)C.Cl>C1(C)C=CC=CC=1>[CH3:2][O:3][C:4](=[O:26])[CH:5]([O:23][CH2:24][CH3:25])[CH2:6][C:7]1[CH:12]=[CH:11][C:10]([CH2:46][CH2:45][N:41]([CH2:42][CH2:44][CH2:4][CH2:5][CH2:6][CH2:7][CH3:8])[C:36]([NH:35][C:29]2[CH:30]=[CH:31][C:32]([F:34])=[CH:33][C:28]=2[F:27])=[O:37])=[CH:9][CH:8]=1

Participants

6

Reactant 4

HCID 313Hydrochloric AcidHCID 81531DiisopropylethylamineHCID 5932582,4-Difluorophenyl isocyanateHCID 698843992-ethoxy-3-[3-(2-heptylamino-ethyl)-phenyl]-propionic acid methyl ester HCl salt

Product 1

HCID 698843623-(4-{2-[3-(2,4-Difluoro-phenyl)-1-heptyl-ureido]-ethyl}-phenyl)-2-ethoxy-propionic acid methyl esterYield 164.5%

Reagents, catalysts & solvents 1

HCID 1140TolueneSolvent

Procedure

To a solution of 2-ethoxy-3-[3-(2-heptylamino-ethyl)-phenyl]-propionic acid methyl ester HCl salt (41 mg, 0.106 mmol), and 2,4-difluorophenylisocyanate (0.17 mmol, 0.0138 mL) in toluene (4.5 mL) was added N,N-diisopropylethylamine (0.32 mmol, 0.055 mL). The mixture was allowed to stir at room temperature for 18 hours, then was poured over 1M HCl (5 mL). The aqueous layer was isolated and extracted with diethyl ether (2×). The organic layers were combined, washed with 2M HCl (2×), brine (2×), dried over anhydrous sodium sulfate, and concentrated to give a clear oil. The crude solid was chromatographed on silica gel (Merck silica gel 60, art#9385-3) eluting with 20% ethyl acetate/hexanes to give 3-(4-{2-[3-(2,4-difluoro-phenyl)-1-heptyl-ureido]-ethyl}-phenyl)-2-ethoxy-propionic acid methyl ester as a clear oil (44 mg, 82%).

Workup

  1. customThe aqueous layer was isolated
  2. extractionextracted with diethyl ether (2×)
  3. washwashed with 2M HCl (2×), brine (2×)
  4. dry with materialdried over anhydrous sodium sulfate
  5. concentrationconcentrated
  6. customto give a clear oil
  7. customThe crude solid was chromatographed on silica gel (Merck silica gel 60, art#9385-3)
  8. washeluting with 20% ethyl acetate/hexanes

Sources & evidence

ORD record
ord-ef472c2905ef43a5847a92465abb3c5a
Source dataset
uspto-grants-2004_03
Patent number
US06699904B2

Reaction notes

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