Toluene → 4-(2-Chloro-5-methylphenylcarbamoyl)-3-[4-cyclopropyl-5-(3-isobutylcyclobutyl)isoxazol-3-yl]butanoic acid

HRID 1912057Notes

Reaction equation

HRID 1912057 reaction equation
[Cl:1][C:2]1[CH:7]=[CH:6][C:5]([CH3:8])=[CH:4][C:3]=1[NH:9][C:10]([CH2:12][CH:13]([C:22]1[C:26]([CH:27]2[CH2:29][CH2:28]2)=[C:25]([CH:30]2[CH2:33][CH:32]([CH2:34][CH:35]([CH3:37])[CH3:36])[CH2:31]2)[O:24][N:23]=1)[CH2:14][C:15]([O:17]C(C)(C)C)=[O:16])=[O:11].C1(C)C=CC=CC=1.FC(F)(F)C(O)=O.[OH-].[Na+]>O>[Cl:1][C:2]1[CH:7]=[CH:6][C:5]([CH3:8])=[CH:4][C:3]=1[NH:9][C:10]([CH2:12][CH:13]([C:22]1[C:26]([CH:27]2[CH2:28][CH2:29]2)=[C:25]([CH:30]2[CH2:31][CH:32]([CH2:34][CH:35]([CH3:37])[CH3:36])[CH2:33]2)[O:24][N:23]=1)[CH2:14][C:15]([OH:17])=[O:16])=[O:11]

Participants

6

Reactant 4

HCID 1140TolueneHCID 6422Trifluoroacetic acidHCID 14798Sodium HydroxideHCID 71135567tert-Butyl 4-(2-chloro-5-methylphenylcarbamoyl)-3-[4-cyclopropyl-5-(3-isobutylcyclobutyl)isoxazol-3-yl]butanoate

Product 1

HCID 711147924-(2-Chloro-5-methylphenylcarbamoyl)-3-[4-cyclopropyl-5-(3-isobutylcyclobutyl)isoxazol-3-yl]butanoic acidYield 92.9%

Reagents, catalysts & solvents 1

HCID 962WaterSolvent

Procedure

tert-Butyl 4-(2-Chloro-5-methylphenylcarbamoyl)-3-[4-cyclopropyl-5-(3-isobutylcyclobutyl)isoxazol-3-yl]butanoate (1.09 g) and toluene (3.2 mL) were mixed. To the mixture was added trifluoroacetic acid (3.2 mL) at ice temperature and the mixture was stirred at RT for 30 min. After water (5 mL) was poured into the reaction mixture dropwise at ice temperature, aqueous 4 N sodium hydroxide was added to the mixture dropwise and the mixture was extracted with ethyl acetate. The organic layer was washed with brine and dried over sodium sulfate. The sodium sulfate was filtered off and the filtrate was concentrated in vacuo. The resultant residue was purified by silica gel column chromatography (Eluent: ethyl acetate/hexane=1/5→1/3→1/2→2/1→methanol/chloroform=1/8) to give the title compound (905 mg). The title compound was analyzed using a chiral column. The retention time of the title compound was 6.6 min., and the optical purity thereof was 94.8% ee.

Workup

  1. additionwas added to the mixture dropwise
  2. extractionthe mixture was extracted with ethyl acetate
  3. washThe organic layer was washed with brine
  4. dry with materialdried over sodium sulfate
  5. filtrationThe sodium sulfate was filtered off
  6. concentrationthe filtrate was concentrated in vacuo
  7. customThe resultant residue was purified by silica gel column chromatography (Eluent: ethyl acetate/hexane=1/5→1/3→1/2→2/1→methanol/chloroform=1/8)

Sources & evidence

ORD record
ord-24c682ea04944c9fb697900288a33625
Source dataset
uspto-grants-2013_12
Patent number
US08604069B2

Reaction notes

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