Acetic Acid → HCID 178470056, compound

HRID 1260698Notes

Reaction equation

HRID 1260698 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].CCN([CH2:20][CH3:21])CC.C[CH2:23][O-:24].[Na+].[C:26]([OH:29])(=[O:28])[CH3:27]>C(Cl)Cl.CCO.C(OC(=O)CC(Cl)=O)C>[CH2:20]([O:28][C:26]([C:27]1[C:23]([OH:24])=[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:29])[CH3:21]

Participants

8

Reactant 4

HCID 176Acetic AcidHCID 8471TriethylamineHCID 2723922Sodium ethoxideHCID 468355001-(2-Amino-4-(trifluoromethyl)phenyl)ethan-1-one

Product 1

HCID 178470056HCID 178470056, compoundYield 72%

Reagents, catalysts & solvents 3

HCID 118931Ethyl 3-chloro-3-oxopropionateCatalystHCID 702EthanolSolventHCID 6344DichloromethaneSolvent2×

Procedure

A solution of 40.6 g (0.2 mol) 1-(2-amino-4-(trifluoromethyl)phenyl)ethanone and 41.6 ml (0.3 mol) NEt3 in DCM (130 ml) was cooled with an ice/water bath. A solution of 38.0 ml (0.3 mmol) ethylchloroformylacetate in DCM (65 ml) was added in drops, wherein the temperature was kept between 10° C. and 15° C. The solution was subsequently stirred for 16 h at RT. It was then quenched with a 1M aq. NaHCO3 sol. (400 ml) and the organic phase was separated, dried over MgSO4 and concentrated in a vacuum. The residue obtained was dissolved in EtOH (350 ml) and 82 ml (0.2 mol, 21%-strength in EtOH) sodium ethylate was added. The mixture was subsequently stirred for 72 h at RT. Acidification was then carried out with 5M aq. acetic acid and the solution was concentrated in a vacuum. The residue was suspended in water (250 ml) and EtOAc (250 ml) and the insoluble precipitate was filtered off. After drying in a vacuum at 40° C., 42.8 g (0.14 mol, 72%) 2-hydroxy-4-methyl-7-(trifluoromethyl)quinoline-3-carboxylic acid-ethyl ester was obtained. The raw product was further converted without additional purification.

Workup

  1. customwas kept between 10° C. and 15° C
  2. customIt was then quenched with a 1M aq. NaHCO3 sol. (400 ml)
  3. customthe organic phase was separated
  4. dry with materialdried over MgSO4
  5. concentrationconcentrated in a vacuum
  6. customThe residue obtained
  7. stirringThe mixture was subsequently stirred for 72 h at RT
  8. concentrationthe solution was concentrated in a vacuum
  9. filtrationEtOAc (250 ml) and the insoluble precipitate was filtered off
  10. customAfter drying in a vacuum at 40° C.

Sources & evidence

ORD record
ord-97f95a550297452ca4e260e9f5783a6f
Source dataset
uspto-grants-2013_06
Patent number
US08470852B2

Reaction notes

Loading…