Triethylamine → N-[2-(2,4-Dimethoxyphenyl)heptyl]-N'-(2-t-butyl-5-carboxyphenyl)urea

HRID 1637540Notes

Reaction equation

HRID 1637540 reaction equation
[CH3:1][O:2][C:3]1[CH:8]=[C:7]([O:9][CH3:10])[CH:6]=[CH:5][C:4]=1[CH:11]([CH2:16][CH2:17][CH2:18][CH2:19][CH3:20])[CH2:12]C(O)=O.C1(P(N=[N+]=[N-])(C2C=CC=CC=2)=[O:28])C=CC=CC=1.C([N:40]([CH2:43]C)CC)C.[C:45]([C:49]1[CH:55]=[CH:54][C:53]([C:56]([O:58]C)=[O:57])=[CH:52][C:50]=1[NH2:51])([CH3:48])([CH3:47])[CH3:46]>C1C=CC=CC=1.C(OCC)(=O)C>[CH3:1][O:2][C:3]1[CH:8]=[C:7]([O:9][CH3:10])[CH:6]=[CH:5][C:4]=1[CH:11]([CH2:16][CH2:17][CH2:18][CH2:19][CH3:20])[CH2:12][NH:40][C:43]([NH:51][C:50]1[CH:52]=[C:53]([C:56]([OH:58])=[O:57])[CH:54]=[CH:55][C:49]=1[C:45]([CH3:46])([CH3:47])[CH3:48])=[O:28]

Participants

7

Reactant 4

HCID 8471TriethylamineHCID 199401P,P-Diphenylphosphinic azideHCID 11959027Methyl 3-amino-4-(tert-butyl)benzoateHCID 193486193-(2,4-Dimethoxyphenyl)octanoic acid

Product 1

HCID 19348747N-[2-(2,4-Dimethoxyphenyl)heptyl]-N'-(2-t-butyl-5-carboxyphenyl)ureaYield 43.3%

Reagents, catalysts & solvents 2

HCID 241BenzeneSolvent2×HCID 8857Ethyl AcetateSolvent

Procedure

A solution of 1.00 g (3.57 mmol) of 3-(2,4-dimethoxyphenyl)octanoic acid (prepared as described in Preparation 3), 982 mg (3.57 mmol) of diphenylphosphoryl azide and 361 mg (3.57 mmol) of triethylamine in 15 ml of benzene was heated under reflux for 2.5 hours. At the end of this time, the reaction temperature was allowed to reduce to room temperature, after which a solution of 739 mg (3.57 mmol) of 2-t-butyl-5-methoxycarbonylaniline (prepared as described in Preparation 5) in 10 ml of benzene was added t o the mixture, and the resulting mixture was heated under reflux for 2 hours and 45 minutes. The reaction mixture was cooled to room temperature, and then the mixture was diluted with ethyl acetate. The diluted solution was washed with 2 N aqueous hydrochloric acid, with water, with a saturated aqueous solution of sodium hydrogencarbonate and with a saturated aqueous solution of sodium chloride, in that order, after which it was dried over anhydrous magnesium sulfate. The solvent was then removed by distillation under reduced pressure, and the resulting residue was purified by column chromatography through 100 g of silica gel, using a 2:1 by volume mixture of ethyl acetate and hexane as the eluent, to give 728 mg of the desired urea derivative as a foam-like substance in a 42% yield. The derivative thus obtained was hydrolyzed in a similar manner to that described in Preparation 7 to give the title compound as a foam-like substance.

Workup

  1. temperatureunder reflux for 2.5 hours
  2. customto reduce to room temperature
  3. temperaturethe resulting mixture was heated
  4. temperatureunder reflux for 2 hours and 45 minutes
  5. washThe diluted solution was washed with 2 N aqueous hydrochloric acid, with water, with a saturated aqueous solution of sodium hydrogencarbonate and with a saturated aqueous solution of sodium chloride, in that order
  6. dry with materialafter which it was dried over anhydrous magnesium sulfate
  7. customThe solvent was then removed by distillation under reduced pressure
  8. customthe resulting residue was purified by column chromatography through 100 g of silica gel
  9. additionby volume mixture of ethyl acetate and hexane as the eluent

Sources & evidence

ORD record
ord-2bbcbd438f4244e290274d7e23a96f74
Source dataset
uspto-grants-2000_03
Patent number
US06040339

Reaction notes

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