Hydrochloric Acid → HCID 67024449, compound

HRID 389139Notes

Reaction equation

HRID 389139 reaction equation
C1N=CN(C(N2C=NC=C2)=O)C=1.[Cl:13][C:14]1[CH:15]=[CH:16][C:17]([O:23][C:24]([CH3:42])([C:26]2[N:30]([CH3:31])[C:29]([C:32]3[CH:37]=[CH:36][CH:35]=[CH:34][C:33]=3[C:38]([F:41])([F:40])[F:39])=[N:28][N:27]=2)[CH3:25])=[C:18]([CH:22]=1)[C:19](O)=[O:20].[BH4-].[Na+].Cl.C(=O)(O)[O-].[Na+]>C1COCC1.C1COCC1.O>[ClH:13].[Cl:13][C:14]1[CH:15]=[CH:16][C:17]([O:23][C:24]([CH3:42])([C:26]2[N:30]([CH3:31])[C:29]([C:32]3[CH:37]=[CH:36][CH:35]=[CH:34][C:33]=3[C:38]([F:39])([F:41])[F:40])=[N:28][N:27]=2)[CH3:25])=[C:18]([CH2:19][OH:20])[CH:22]=1

Participants

8

Reactant 5

HCID 313Hydrochloric AcidHCID 682631,1'-CarbonyldiimidazoleHCID 516892Sodium BicarbonateHCID 4311764Sodium borohydrideHCID 58244031HCID 58244031, compound

Product 1

HCID 67024449HCID 67024449, compoundYield 116.1%

Reagents, catalysts & solvents 2

HCID 8028TetrahydrofuranSolventHCID 21881883Oxolane--water (1/1)Solvent

Procedure

CDI (144 mg) was added to a solution of 5-chloro-2-(1-methyl-1-{4-methyl-5-[2-(trifluoromethyl)phenyl]-4H-1,2,4-triazol-3-yl}ethoxy)benzoic acid (300 mg) in THF (3 ml), followed by stirring at room temperature for 1.5 hours. The reaction solution was added dropwise at 0° C. to a mixed solution of sodium borohydride in THF/water (6 ml, 1:1) under a nitrogen atmosphere, followed by stirring at room temperature for one hour. 1M hydrochloric acid was added to the reaction solution to cease the reaction and then neutralized with saturated aqueous sodium bicarbonate. After extraction with ethyl acetate, the organic layer was washed with saturated brine and dried over anhydrous magnesium sulfate and the solvent was evaporated under reduced pressure. The resulting residue was purified by silica gel column chromatography (chloroform:methanol=95:5), the resulting solid (190 mg) was dissolved in ethyl acetate, and 4M hydrogen chloride-ethyl acetate was added thereto, followed by stirred for 30 minutes. The solution was concentrated under reduced pressure and powdered with diisopropylether to obtain [5-chloro-2-(1-methyl-1-{4-methyl-5-[2-(trifluoromethyl)phenyl]-4H-1,2,4-triazol-3-yl}ethoxy)phenyl]methanol monohydrochloride (183 mg) as a white powder.

Workup

  1. stirringby stirring at room temperature for one hour
  2. customthe reaction
  3. extractionAfter extraction with ethyl acetate
  4. washthe organic layer was washed with saturated brine
  5. dry with materialdried over anhydrous magnesium sulfate
  6. customthe solvent was evaporated under reduced pressure
  7. customThe resulting residue was purified by silica gel column chromatography (chloroform:methanol=95:5)
  8. dissolutionthe resulting solid (190 mg) was dissolved in ethyl acetate
  9. addition4M hydrogen chloride-ethyl acetate was added
  10. stirringby stirred for 30 minutes
  11. concentrationThe solution was concentrated under reduced pressure

Sources & evidence

ORD record
ord-2a52aadfd8704db9a97d4ea539a64e96
Source dataset
uspto-grants-2013_02
Patent number
US08377923B2

Reaction notes

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