Hydrochloric Acid → 1-(5-Chloro-6-methyl-1H-benzoimidazol-2-yl)-2,2,2-trifluoro-ethanol

HRID 230453

Reaction equation

HRID 230453 reaction equation
[Cl:1][C:2]1[CH:3]=[C:4]([NH2:10])[C:5]([NH2:9])=[CH:6][C:7]=1[CH3:8].[F:11][C:12]([F:19])([F:18])[CH:13]([OH:17])[C:14](O)=O.Cl.C(=O)(O)[O-].[Na+]>O.C(OCC)(=O)C>[Cl:1][C:2]1[C:7]([CH3:8])=[CH:6][C:5]2[NH:9][C:14]([CH:13]([OH:17])[C:12]([F:19])([F:18])[F:11])=[N:10][C:4]=2[CH:3]=1

Participants

7

Reactant 4

HCID 313Hydrochloric AcidHCID 2448963,3,3-Trifluoro-2-hydroxypropanoic acidHCID 516892Sodium BicarbonateHCID 28014684-Chloro-5-methylbenzene-1,2-diamine

Product 1

HCID 596822781-(5-Chloro-6-methyl-1H-benzoimidazol-2-yl)-2,2,2-trifluoro-ethanol

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 8857Ethyl AcetateSolvent

Conditions

Temperature
108 °C

Procedure

4-Chloro-5-methyl-benzene-1,2-diamine (5.06 g; 32.3 mmoles) and 3,3,3-trifluoro-2-hydroxy-propionic acid (7.11 g; 49.4 mmoles) were suspended in 6N HCl (12 mL; 72 mmoles) under a nitrogen atmosphere. The reaction was stirred vigorously and heated to 108° C. for 18 hrs, then cooled to room temperature. The reaction was diluted with water (100 mL) and with ethyl acetate (100 mL), then sodium bicarbonate (9.12 g; 109 mmoles) was added slowly and in portions to quench the reaction. The aqueous layer was separated and extracted with ethyl acetate (3×40 mL). The extracts were combined, washed with water (30 mL) and brine (30 mL), then dried over Na2SO4. The filtrate was concentrated in vacuo to yield a crude brown solid which was then purified by column chromatography (SiO2; 30% ethyl cetate/CH2Cl2) to yield the title compound as a purple/brown solid.

Workup

  1. temperaturecooled to room temperature
  2. customto quench
  3. customthe reaction
  4. customThe aqueous layer was separated
  5. extractionextracted with ethyl acetate (3×40 mL)
  6. washwashed with water (30 mL) and brine (30 mL)
  7. dry with materialdried over Na2SO4
  8. concentrationThe filtrate was concentrated in vacuo
  9. customto yield a crude brown solid which
  10. customwas then purified by column chromatography (SiO2; 30% ethyl cetate/CH2Cl2)

Sources & evidence

ORD record
ord-752900ee54134e6894e6296fd24c630d
Source dataset
uspto-grants-2009_07
Patent number
US07566733B2

Linked notes

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