2-Benzoylcyclohexanone → 2-(2-Benzoyl-phenylamino)-3-{4-[2-(5-methyl-2-phenyl-oxazol-4-yl)-ethoxy]-naphthalen-1-yl}-propionic acid ethyl ester

HRID 479127

Reaction equation

HRID 479127 reaction equation
[CH2:1]([O:3][C:4](=[O:33])[CH:5]([NH2:32])[CH2:6][C:7]1[C:16]2[C:11](=[CH:12][CH:13]=[CH:14][CH:15]=2)[C:10]([O:17][CH2:18][CH2:19][C:20]2[N:21]=[C:22]([C:26]3[CH:31]=[CH:30][CH:29]=[CH:28][CH:27]=3)[O:23][C:24]=2[CH3:25])=[CH:9][CH:8]=1)[CH3:2].[C:34]([CH:42]1[CH2:47][CH2:46][CH2:45][CH2:44][C:43]1=O)(=[O:41])[C:35]1[CH:40]=[CH:39][CH:38]=[CH:37][CH:36]=1>C1(OC)C=CC=CC=1.[Pd]>[CH2:1]([O:3][C:4](=[O:33])[CH:5]([NH:32][C:36]1[CH:37]=[CH:38][CH:39]=[CH:40][C:35]=1[C:34](=[O:41])[C:42]1[CH:43]=[CH:44][CH:45]=[CH:46][CH:47]=1)[CH2:6][C:7]1[C:16]2[C:11](=[CH:12][CH:13]=[CH:14][CH:15]=2)[C:10]([O:17][CH2:18][CH2:19][C:20]2[N:21]=[C:22]([C:26]3[CH:31]=[CH:30][CH:29]=[CH:28][CH:27]=3)[O:23][C:24]=2[CH3:25])=[CH:9][CH:8]=1)[CH3:2]

Participants

5

Reactant 2

HCID 2756272-BenzoylcyclohexanoneHCID 695578292-Amino-3-{4-[2-(5-methyl-2-phenyl-oxazol-4-yl)-ethoxy]-naphthalen-1-yl}-propionic acid ethyl ester

Product 1

HCID 695571212-(2-Benzoyl-phenylamino)-3-{4-[2-(5-methyl-2-phenyl-oxazol-4-yl)-ethoxy]-naphthalen-1-yl}-propionic acid ethyl esterYield 15.5%

Reagents, catalysts & solvents 2

HCID 23938PalladiumCatalystHCID 7519AnisoleSolvent

Conditions

Temperature
182.5 °C

Procedure

0.345 g of 2-Amino-3-{4-[2-(5-methyl-2-phenyl-oxazol-4-yl)-ethoxy]-naphthalen-1-yl}-propionic acid ethyl ester was dissolved in 6 ml of anisole and treated successively with 0.181 g (1.15 eq.) of 2-benzoyl-cyclohexanone and 60 mg of Pd/C (10%) and heated under Ar to 180-185° C. After 80 Min., additional 60 mg of fresh catalyst was added and heating continued for another 3.5 h. Cooling to RT, pouring onto crashed ice, twofold extraction with AcOEt, washing with water, drying over sodium sulfate, and purification by flash chromatography (SiO2, hexane/AcOEt 7/3) produced 0.075 g of the title compound in the less polar fractions and 0.285 g of intermediate enamine, which was processed once again as just described. Final purification left a combined crop of 0.221 g of 2-(2-benzoyl-phenylamino)-3-{4-[2-(5-methyl-2-phenyl-oxazol-4-yl)-ethoxy]-naphthalen-1-yl}-propionic acid ethyl ester as yellow, sticky oil.

Workup

  1. temperatureheating
  2. temperatureCooling to RT
  3. additionpouring
  4. extractionice, twofold extraction with AcOEt
  5. washwashing with water
  6. dry with materialdrying over sodium sulfate, and purification by flash chromatography (SiO2, hexane/AcOEt 7/3)

Sources & evidence

ORD record
ord-5090fdba31e7417fbcbb4338bb908c19
Source dataset
uspto-grants-2003_11
Patent number
US06642389B2

Linked notes

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