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

HRID 1912082Notes

Reaction equation

HRID 1912082 reaction equation
[Cl:1][C:2]1[CH:7]=[CH:6][C:5]([NH:8][C:9]([CH2:11][CH:12]([C:19]2[C:23]([CH:24]3[CH2:26][CH2:25]3)=[C:22]([CH:27]3[CH2:30][CH:29]([CH2:31][C:32]([CH3:35])([CH3:34])[CH3:33])[CH2:28]3)[O:21][N:20]=2)[CH2:13][CH2:14][C:15]([O:17]C)=[O:16])=[O:10])=[C:4]([CH3:36])[CH:3]=1.Br.C([O-])(=O)C.[Na+]>C(O)(=O)C>[Cl:1][C:2]1[CH:7]=[CH:6][C:5]([NH:8][C:9]([CH2:11][CH:12]([C:19]2[C:23]([CH:24]3[CH2:25][CH2:26]3)=[C:22]([CH:27]3[CH2:28][CH:29]([CH2:31][C:32]([CH3:34])([CH3:33])[CH3:35])[CH2:30]3)[O:21][N:20]=2)[CH2:13][CH2:14][C:15]([OH:17])=[O:16])=[O:10])=[C:4]([CH3:36])[CH:3]=1

Participants

5

Reactant 3

HCID 260Hydrogen BromideHCID 517045Sodium AcetateHCID 71114755Methyl 5-(4-chloro-2-methylphenylcarbamoyl)-4-{4-cyclopropyl-5-[3-(2,2-dimethylpropyl)cyclobutyl]isoxazol-3-yl}valerate

Product 1

HCID 711147445-(4-Chloro-2-methylphenylcarbamoyl)-4-{4-cyclopropyl-5-[3-(2,2-dimethylpropyl)cyclobutyl]isoxazol-3-yl}valeric acidYield 69.6%

Reagents, catalysts & solvents 1

HCID 176Acetic AcidSolvent

Conditions

Temperature
60 °C

Procedure

Methyl 5-(4-chloro-2-methylphenylcarbamoyl)-4-{4-cyclopropyl-5-[3-(2,2-dimethylpropyl)cyclobutyl]isoxazol-3-yl}valerate (72.5 mg) and acetic acid (0.725 mL) were mixed. To the mixture was added 48 w/v % hydrobromic acid (0.363 mL) at RT. The mixture was stirred at 60° C., and then to the reaction mixture was added sodium acetate (287 mg) at ice temperature. The mixture was extracted 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=1/20/0.05) to give the title compound (49.1 mg). The specific optical rotation value of the title compound was [α]D25=+32.0° (c=1.00, methanol). The title compound was analyzed using a chiral column. The retention time of the title compound was 26.8 min., and the optical purity thereof was 94.8% ee.

Workup

  1. extractionThe mixture was extracted with ethyl acetate
  2. washThe organic layer was washed with water and brine
  3. dry with materialdried over magnesium sulfate
  4. filtrationThe magnesium sulfate was filtered off
  5. concentrationthe filtrate was concentrated in vacuo
  6. customThe resultant residue was purified by preparative chromatography (Eluent: methanol/chloroform/acetic acid=1/20/0.05)

Sources & evidence

ORD record
ord-87a47da439664b3ab572411747fd9dbf
Source dataset
uspto-grants-2013_12
Patent number
US08604069B2

Reaction notes

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