Hydrochloric Acid → 2-(Methoxymethyl)-4-methyl-7-(trifluoromethyl)quinoline-3-carboxylic acid methyl ester

HRID 2093715Notes

Reaction equation

HRID 2093715 reaction equation
[NH2:1][C:2]1[CH:7]=[C:6]([C:8]([F:11])([F:10])[F:9])[CH:5]=[CH:4][C:3]=1[C:12](=O)[CH3:13].Cl.[Li+].[OH-].C[CH2:19][O:20][C:21]([CH3:23])=[O:22].CCCCCC.[CH3:30][CH2:31][O:32][C:33](C)=O>O.CO>[CH3:19][O:20][C:21]([C:23]1[C:30]([CH2:31][O:32][CH3:33])=[N:1][C:2]2[C:3]([C:12]=1[CH3:13])=[CH:4][CH:5]=[C:6]([C:8]([F:11])([F:10])[F:9])[CH:7]=2)=[O:22]

Participants

8

Reactant 5

HCID 313Hydrochloric AcidHCID 3939Lithium HydroxideHCID 8857Ethyl Acetate2×HCID 21226206Ethyl acetate hexaneHCID 468355001-(2-Amino-4-(trifluoromethyl)phenyl)ethan-1-one

Product 1

HCID 665840322-(Methoxymethyl)-4-methyl-7-(trifluoromethyl)quinoline-3-carboxylic acid methyl esterYield 16%

Reagents, catalysts & solvents 2

HCID 887MethanolSolventHCID 962WaterSolvent2×

Conditions

Temperature
75 °C

Procedure

A mixture of 4.0 g (19.7 mmol) 1-(2-amino-4-(trifluoromethyl)phenyl)ethanone, 11.5 ml (98.5 mmol) 4-chloro-diacetic acid ethyl ester and 1.7 ml (19.7 mmol) conc. hydrochloric acid was heated to 75° C. for 6 min in a sealed vessel by microwaves (50 W). The mixture was subsequently diluted with EtOAc and water. The organic phase was separated, washed with a 1M aq. NaHCO3 sol., dried over MgSO4 and concentrated in a vacuum. The raw product (7.47 g) obtained after CC (EtOAc/hexane 3:17) of the residue was dissolved in MeOH (76 ml) and 35.3 ml (70.6 mmol) of a 2M aq. LiOH sol. was added. The mixture was subsequently stirred for 16 h at RT and heated to 60° C. for a further 24 h. After cooling to RT, the mixture was diluted with water and EtOAc. The organic phase was separated, dried over MgSO4 and concentrated in a vacuum. After CC (EtOAc/hexane 1:3) of the residue, 985 mg (3.1 mmol, 16%) 2-(methoxymethyl)-4-methyl-7-(trifluoromethyl)quinoline-3-carboxylic acid methyl ester was obtained.

Workup

  1. customThe organic phase was separated
  2. washwashed with a 1M aq. NaHCO3 sol.
  3. dry with materialdried over MgSO4
  4. concentrationconcentrated in a vacuum
  5. customThe raw product (7.47 g) obtained after CC (EtOAc/hexane 3:17) of the residue
  6. temperatureheated to 60° C. for a further 24 h
  7. temperatureAfter cooling to RT
  8. customThe organic phase was separated
  9. dry with materialdried over MgSO4
  10. concentrationconcentrated in a vacuum

Sources & evidence

ORD record
ord-02d2e684ca174c26897172c24b2dff2d
Source dataset
uspto-grants-2013_05
Patent number
US08445512B2

Reaction notes

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