Water → HCID 58288273, compound

HRID 1476145Notes

Reaction equation

HRID 1476145 reaction equation
[Cl:1][C:2]1[CH:7]=[CH:6][C:5]([CH:8]([CH2:14][CH3:15])[CH2:9][C:10]([O:12]C)=[O:11])=[CH:4][C:3]=1[NH:16][C:17](=[O:32])[C@H:18]([C:25]1[CH:30]=[CH:29][C:28]([Cl:31])=[CH:27][CH:26]=1)[C@@H:19]([CH3:24])[C:20]([F:23])([F:22])[F:21].S(=O)(=O)(O)O.O>C(O)(=O)C>[Cl:1][C:2]1[CH:7]=[CH:6][C:5]([CH:8]([CH2:14][CH3:15])[CH2:9][C:10]([OH:12])=[O:11])=[CH:4][C:3]=1[NH:16][C:17](=[O:32])[C@H:18]([C:25]1[CH:30]=[CH:29][C:28]([Cl:31])=[CH:27][CH:26]=1)[C@@H:19]([CH3:24])[C:20]([F:23])([F:22])[F:21]

Participants

5

Reactant 3

HCID 962WaterHCID 1118Sulfuric AcidHCID 58288345HCID 58288345, compound

Product 1

HCID 58288273HCID 58288273, compound

Reagents, catalysts & solvents 1

HCID 176Acetic AcidSolvent

Conditions

Temperature
140 °C

Procedure

650 mg (1.33 mmol) of methyl 3-(4-chloro-3-{[(2S,3R)-2-(4-chlorophenyl)-4,4,4-trifluoro-3-methylbutanoyl]amino}phenyl)pentanoate (diastereomer mixture) were dissolved in 2 ml of acetic acid, 1 ml of 30% strength sulphuric acid was added and the mixture was heated at reflux (bath temperature about 140° C.). After 1.5 h, the reaction mixture was cooled and added to water. The mixture was extracted three times with ethyl acetate. The combined organic phases were washed with sat. sodium bicarbonate solution and sat. sodium chloride solution, dried over magnesium sulphate and concentrated under reduced pressure. After drying under high vacuum, the residue was purified by chromatography on silica gel (mobile phase cyclohexane/ethyl acetate 50:1). This gave 600 mg of the target product (95% of theory).

Workup

  1. temperaturethe mixture was heated
  2. temperaturethe reaction mixture was cooled
  3. extractionThe mixture was extracted three times with ethyl acetate
  4. washThe combined organic phases were washed with sat. sodium bicarbonate solution and sat. sodium chloride solution
  5. dry with materialdried over magnesium sulphate
  6. concentrationconcentrated under reduced pressure
  7. customAfter drying under high vacuum
  8. customthe residue was purified by chromatography on silica gel (mobile phase cyclohexane/ethyl acetate 50:1)

Sources & evidence

ORD record
ord-7c9143991ac948269da367674cb00c62
Source dataset
uspto-grants-2015_04
Patent number
US09018414B2

Reaction notes

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