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

HRID 47794Notes

Reaction equation

HRID 47794 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.C([N:30]([CH2:34][CH3:35])[CH:31]([CH3:33])C)(C)C.[F:36][C:37]1[CH:42]=[C:41]([F:43])[CH:40]=[CH:39][C:38]=1[CH2:44][C:45](Cl)=[O:46].Cl>C(Cl)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][C:10]([CH2:35][CH2:34][N:30]([C:45](=[O:46])[CH2:44][C:38]2[CH:39]=[CH:40][C:41]([F:43])=[CH:42][C:37]=2[F:36])[CH2:31][CH2:33][CH2:4][CH2:5][CH2:6][CH2:7][CH3:8])=[CH:9][CH:8]=1

Participants

6

Reactant 4

HCID 313Hydrochloric AcidHCID 81531DiisopropylethylamineHCID 152316062,4-Difluorophenylacetyl chlorideHCID 698843992-ethoxy-3-[3-(2-heptylamino-ethyl)-phenyl]-propionic acid methyl ester HCl salt

Product 1

HCID 121254603-[4-(2-{[(2,4-Difluoro-phenyl)-acetyl]-heptyl-amino}-ethyl)-phenyl]-2-ethoxy-propionic acid methyl esterYield 131.8%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent2×

Procedure

To a solution of 2-ethoxy-3-[3-(2-heptylamino-ethyl)-phenyl]-propionic acid methyl ester HCl salt (43 mg, 0.11 mmol) and N,N-diisopropylethylamine (0.33 mmol, 0.058 mL) in anhydrous methylene chloride (2 mL) was added 2,4-difluorophenylacetyl chloride (0.128 mmol) in anhydrous methylene chloride (2 mL). The mixture was allowed to stir at room temperature for 16 hours. Then was poured over 1 M HCl (5 mL). The aqueous layer was isolated and extracted with methylene chloride (1×). The organic layers were combined, washed with 2 M HCl (1×), brine (1×), dried over anhydrous sodium sulfate, and concentrated to give a clear oil. The crude product was chromatographed on silica gel (Merck silica gel 60, art#9385-3) eluting with 20% ethyl acetate/hexanes to give 3-[4-(2-{[(2,4-difluoro-phenyl)-acetyl]-heptyl-amino}-ethyl)-phenyl]-2-ethoxy-propionic acid methyl ester as a clear oil (36.5 mg, 66%).

Workup

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

Sources & evidence

ORD record
ord-01816aae19f448beb6bcc48bd7fb631c
Source dataset
uspto-grants-2004_03
Patent number
US06699904B2

Reaction notes

Loading…