Lithium Hydroxide → HCID 58111794, compound

HRID 1042493Notes

Reaction equation

HRID 1042493 reaction equation
[OH:1][C:2]1[CH:10]=[C:9]([C:11]([F:14])([F:13])[F:12])[CH:8]=[CH:7][C:3]=1[C:4]([OH:6])=O.C(=O)([O-])[O-].[K+].[K+].I[CH:22]([CH2:24][CH3:25])[CH3:23].[Li+].[OH-].Cl.[CH3:29][NH:30][O:31][CH3:32].CN1CCOCC1.Cl.CN(C)CCCN=C=NCC>CN(C=O)C.CCOC(C)=O.C(Cl)Cl>[CH:22]([O:1][C:2]1[CH:10]=[C:9]([C:11]([F:14])([F:13])[F:12])[CH:8]=[CH:7][C:3]=1[C:4]([N:30]([O:31][CH3:32])[CH3:29])=[O:6])([CH2:24][CH3:25])[CH3:23]

Participants

11

Reactant 7

HCID 3939Lithium HydroxideHCID 79724-MethylmorpholineHCID 105592-IodobutaneHCID 11430Potassium CarbonateHCID 81138Methanamine, N-methoxy-, hydrochloride (1:1)HCID 1645782-Hydroxy-4-(trifluoromethyl)benzoic acidHCID 27239391,3-Propanediamine, N'-(ethylcarbonimidoyl)-N,N-dimethyl-, monohydrochloride

Product 1

HCID 58111794HCID 58111794, compound

Reagents, catalysts & solvents 3

HCID 6228DimethylformamideSolventHCID 6344DichloromethaneSolventHCID 8857Ethyl AcetateSolvent3×

Conditions

Temperature
110 °C

Procedure

A mixture of 2-hydroxy-4-trifluoromethyl-benzoic acid (300 mg, 1.45 mmol) in DMF was added potassium carbonate (442 mg, 3.20 mmol) followed by 2-iodobutane (589 mg, 3.2 mmol). The mixture was stirred for 48 hours at 110° C. and then diluted with EtOAc. The organic layer was washed with 1N HCl, water, and brine, dried over anhydrous magnesium sulfate, filtered and concentrated under reduced pressure. The crude residue was dissolved in THF (2 ml) and then added a solution of 0.5 N-LiOH (2 eq). The mixture was stirred for 2 hours at room temperature and then diluted with EtOAc. The organic layer was washed with 1N HCl, water, and brine, dried over anhydrous magnesium sulfate, filtered and concentrated under reduced pressure. The crude residue and N,O-dimethylhydroxylamine hydrochloride (316 mg, 0.16 mmol) in CH2Cl2 (5 mL) was added N-methylmorpholine (0.176 ml, 0.160 mmol). The mixture was stirred for 5 minutes, to which were added N-(3-dimethylaminopropyl)-N′-ethylcarbodiimide hydrochloride (316 mg, 0.160 mmol). The mixture was stirred for 2 hours at room temperature and then diluted with EtOAc. The organic layer was washed with 1N HCl, water, and brine, dried over anhydrous magnesium sulfate, filtered and concentrated under reduced pressure. The crude residue was purified by chromatography to give the title compound. (374 mg, 84%).

Workup

  1. washThe organic layer was washed with 1N HCl, water, and brine
  2. dry with materialdried over anhydrous magnesium sulfate
  3. filtrationfiltered
  4. concentrationconcentrated under reduced pressure
  5. dissolutionThe crude residue was dissolved in THF (2 ml)
  6. stirringThe mixture was stirred for 2 hours at room temperature
  7. washThe organic layer was washed with 1N HCl, water, and brine
  8. dry with materialdried over anhydrous magnesium sulfate
  9. filtrationfiltered
  10. concentrationconcentrated under reduced pressure
  11. stirringThe mixture was stirred for 5 minutes, to which
  12. stirringThe mixture was stirred for 2 hours at room temperature
  13. washThe organic layer was washed with 1N HCl, water, and brine
  14. dry with materialdried over anhydrous magnesium sulfate
  15. filtrationfiltered
  16. concentrationconcentrated under reduced pressure
  17. customThe crude residue was purified by chromatography

Sources & evidence

ORD record
ord-7549a0a342b341f39ce39c34177ba85e
Source dataset
uspto-grants-2013_10
Patent number
US08557872B2

Reaction notes

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