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

HRID 47814

Reaction equation

HRID 47814 reaction equation
[CH2:1]([NH:8][CH2:9][CH2:10][C:11]1[CH:16]=[CH:15][C:14]([CH2:17][C:18]([CH3:23])([CH3:22])[C:19]([OH:21])=[O:20])=[CH:13][CH:12]=1)[CH2:2][CH2:3][CH2:4][CH2:5][CH2:6][CH3:7].C(N(CC)C(C)C)(C)C.[F:33][C:34]1[CH:39]=[C:38]([F:40])[CH:37]=[CH:36][C:35]=1[N:41]=[C:42]=[O:43].Cl>C1(C)C=CC=CC=1>[F:33][C:34]1[CH:39]=[C:38]([F:40])[CH:37]=[CH:36][C:35]=1[NH:41][C:42](=[O:43])[N:8]([CH2:9][CH2:10][C:11]1[CH:12]=[CH:13][C:14]([CH2:17][C:18]([CH3:22])([CH3:23])[C:19]([OH:21])=[O:20])=[CH:15][CH:16]=1)[CH2:1][CH2:2][CH2:3][CH2:4][CH2:5][CH2:6][CH3:7]

Participants

6

Reactant 4

HCID 313Hydrochloric AcidHCID 81531DiisopropylethylamineHCID 5932582,4-Difluorophenyl isocyanateHCID 234312233-[4-(2-Heptylamino-ethyl)-phenyl]-2,2-dimethyl-propionic acid

Product 1

HCID 234312483-(4-{2-[3-(2,4-Difluoro-phenyl)-1-heptyl-ureido]-ethyl}-phenyl)-2,2-dimethyl-propionic acid

Reagents, catalysts & solvents 1

HCID 1140TolueneSolvent

Procedure

To a solution of 3-[4-(2-heptylamino-ethyl)-phenyl]-2,2-dimethyl-propionic acid (23 mg, 0.072 mmol), and N,N-diisopropylethylamine (0.152 mmol, 0.0264 mL) dissolved in toluene (2 mL) was added 2,4-difluorophenylisocyanate (0.0796 mmol, 0.0094 mL). The mixture was allowed to stir at room temperature for 72 hours, then was poured over 1 M HCl (5 mL). The aqueous layer was isolated and extracted with diethyl ether (2×). The organic layers were combined, washed with 2 M HCl (2×), brine (2×), dried over anhydrous sodium sulfate, and concentrated to give a clear film. The crude product was chromatographed on silica gel (Merck silica gel 60, art#9385-3) eluting with 5% methanol/methylene chloride to give 3-(4-{2-[3-(2,4-difluoro-phenyl)-1-heptyl-ureido]-ethyl}-phenyl)-2,2-dimethyl-propionic acid as a clear film (18.5 mg, 54%).

Workup

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

Sources & evidence

ORD record
ord-4da504f5584d4aca81c5c94b94a488c0
Source dataset
uspto-grants-2004_03
Patent number
US06699904B2

Linked notes

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