Tetrahydrofuran → HCID 118343002, compound

HRID 2202759Notes

Reaction equation

HRID 2202759 reaction equation
[OH-].[Na+].[Cl:3][C:4]1[CH:5]=[N:6][CH:7]=[C:8]([Cl:43])[C:9]=1[C:10](=[O:42])[CH2:11][N:12]([CH2:37][C:38]([CH3:41])([CH3:40])[CH3:39])[C:13]([C:15]1[CH:16]=[N:17][N:18]([C@H:24]2[CH2:29][CH2:28][C@H:27]([C:30]([O:32]CC)=[O:31])[C:26]([CH3:36])([CH3:35])[CH2:25]2)[C:19]=1[C:20]([F:23])([F:22])[F:21])=[O:14].C1COCC1>CCO>[Cl:3][C:4]1[CH:5]=[N:6][CH:7]=[C:8]([Cl:43])[C:9]=1[C:10](=[O:42])[CH2:11][N:12]([CH2:37][C:38]([CH3:41])([CH3:40])[CH3:39])[C:13]([C:15]1[CH:16]=[N:17][N:18]([C@H:24]2[CH2:29][CH2:28][C@H:27]([C:30]([OH:32])=[O:31])[C:26]([CH3:36])([CH3:35])[CH2:25]2)[C:19]=1[C:20]([F:23])([F:22])[F:21])=[O:14]

Participants

5

Reactant 3

HCID 8028TetrahydrofuranHCID 14798Sodium HydroxideHCID 118383383HCID 118383383, compound

Product 1

HCID 118343002HCID 118343002, compoundYield 88%

Reagents, catalysts & solvents 1

HCID 702EthanolSolvent

Conditions

Temperature
60 °C

Procedure

NaOH (1.6 mL of a 1.0 M aqueous solution, 1.6 mmol) was added to a stirring solution of ethyl (1S,4S)-4-(4-((2-(3,5-dichloro-4-pyridinyl)-2-oxoethyl)(2,2-dimethylpropyl)carbamoyl)-5-(trifluoromethyl)-1H-pyrazol-1-yl)-2,2-dimethylcyclohexanecarboxylate (0.098 g, 0.16 mmol, from Step 2), THF (1.6 mL), and EtOH (1.6 mL), and then the reaction mixture was heated at 60° C. After stirring for 40 h, the reaction mixture was allowed to cool to room temperature and then concentrated under reduced pressure. The residue was dissolved with water (10 mL), concentrated hydrochloric acid (10 drops) was added to the solution, the resulting heterogeneous mixture was filtered, the filter cake washed with water, dissolved with Et2O, the solution was filtered, and the filtrate was concentrated under reduced pressure. The residue was dissolved with DCM, the solution was filtered, and the filtrate was concentrated under reduced pressure to give (1S,4S)-4-(4-((2-(3,5-dichloro-4-pyridinyl)-2-oxoethyl)(2,2-dimethylpropyl)carbamoyl)-5-(trifluoromethyl)-1H-pyrazol-1-yl)-2,2-dimethylcyclohexanecarboxylic acid (0.082 g, 88% yield) as a colorless solid.

Workup

  1. temperatureto cool to room temperature
  2. concentrationconcentrated under reduced pressure
  3. dissolutionThe residue was dissolved with water (10 mL), concentrated hydrochloric acid (10 drops)
  4. additionwas added to the solution
  5. filtrationthe resulting heterogeneous mixture was filtered
  6. washthe filter cake washed with water
  7. dissolutiondissolved with Et2O
  8. filtrationthe solution was filtered
  9. concentrationthe filtrate was concentrated under reduced pressure
  10. dissolutionThe residue was dissolved with DCM
  11. filtrationthe solution was filtered
  12. concentrationthe filtrate was concentrated under reduced pressure

Sources & evidence

ORD record
ord-b39019bdadaa47678b565aa73ce2db5d
Source dataset
uspto-grants-2016_06
Patent number
US09365522B2

Reaction notes

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