Acetic Acid → 5-(2-Chloro-4-methylphenylcarbamoyl)-4-{4-cyclopropyl-5-[3-(2,2-dimethylpropyl)cyclobutyl]isoxazol-3-yl}valeric acid

HRID 1912084Notes

Reaction equation

HRID 1912084 reaction equation
[Cl:1][C:2]1[CH:7]=[C:6]([CH3:8])[CH:5]=[CH:4][C:3]=1[NH:9][C:10]([CH2:12][CH:13]([C:20]1[C:24]([CH:25]2[CH2:27][CH2:26]2)=[C:23]([CH:28]2[CH2:31][CH:30]([CH2:32][C:33]([CH3:36])([CH3:35])[CH3:34])[CH2:29]2)[O:22][N:21]=1)[CH2:14][CH2:15][C:16]([O:18]C)=[O:17])=[O:11].C(O)(=O)C.Br.C([O-])(=O)C.[Na+]>O>[Cl:1][C:2]1[CH:7]=[C:6]([CH3:8])[CH:5]=[CH:4][C:3]=1[NH:9][C:10]([CH2:12][CH:13]([C:20]1[C:24]([CH:25]2[CH2:26][CH2:27]2)=[C:23]([CH:28]2[CH2:29][CH:30]([CH2:32][C:33]([CH3:36])([CH3:35])[CH3:34])[CH2:31]2)[O:22][N:21]=1)[CH2:14][CH2:15][C:16]([OH:18])=[O:17])=[O:11]

Participants

6

Reactant 4

HCID 176Acetic AcidHCID 260Hydrogen BromideHCID 517045Sodium AcetateHCID 71114721Methyl 5-(2-chloro-4-methylphenylcarbamoyl)-4-{4-cyclopropyl-5-[3-(2,2-dimethylpropyl)cyclobutyl]isoxazol-3-yl}valerate

Product 1

HCID 711147225-(2-Chloro-4-methylphenylcarbamoyl)-4-{4-cyclopropyl-5-[3-(2,2-dimethylpropyl)cyclobutyl]isoxazol-3-yl}valeric acidYield 92.1%

Reagents, catalysts & solvents 1

HCID 962WaterSolvent

Procedure

Methyl 5-(2-chloro-4-methylphenylcarbamoyl)-4-{4-cyclopropyl-5-[3-(2,2-dimethylpropyl)cyclobutyl]isoxazol-3-yl}valerate (63.3 mg) and acetic acid (0.6 mL) were mixed. To the mixture was added 48 w/v % hydrobromic acid (0.3 mL) at 10° C. The mixture was stirred at RT, and further stirred at 50° C. To the reaction mixture were added sodium acetate (250 mg) and water at ice temperature. The mixture was extracted twice with ethyl acetate. The organic layer was washed with water and brine, then dried over magnesium sulfate. The magnesium sulfate was filtered off and the filtrate was concentrated in vacuo. The resultant residue was purified by preparative chromatography (Eluent: methanol/chloroform/acetic acid=1/20/0.1) to give the title compound (56.7 mg).

Workup

  1. stirringfurther stirred at 50° C
  2. extractionThe mixture was extracted twice with ethyl acetate
  3. washThe organic layer was washed with water and brine
  4. dry with materialdried over magnesium sulfate
  5. filtrationThe magnesium sulfate was filtered off
  6. concentrationthe filtrate was concentrated in vacuo
  7. customThe resultant residue was purified by preparative chromatography (Eluent: methanol/chloroform/acetic acid=1/20/0.1)

Sources & evidence

ORD record
ord-f4572a9c65654a82986edaddda496f23
Source dataset
uspto-grants-2013_12
Patent number
US08604069B2

Reaction notes

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