Trifluoroacetic acid → {7-[4-Methyl-2-(4-trifluoromethyl-phenyl)-thiazol-5-ylmethoxy]-2-oxo-3,4-dihydro-2H-quinolin-1-yl}-acetic acid

HRID 490772Notes

Reaction equation

HRID 490772 reaction equation
[CH3:1][C:2]1[N:3]=[C:4]([C:20]2[CH:25]=[CH:24][C:23]([C:26]([F:29])([F:28])[F:27])=[CH:22][CH:21]=2)[S:5][C:6]=1[CH2:7][O:8][C:9]1[CH:18]=[C:17]2[C:12]([CH2:13][CH2:14][C:15](=[O:19])[NH:16]2)=[CH:11][CH:10]=1.[H-].[Na+].Br[CH2:33][C:34]([O:36]C(C)(C)C)=[O:35].C(O)(C(F)(F)F)=O>CN(C=O)C.O.C(Cl)Cl>[CH3:1][C:2]1[N:3]=[C:4]([C:20]2[CH:25]=[CH:24][C:23]([C:26]([F:29])([F:27])[F:28])=[CH:22][CH:21]=2)[S:5][C:6]=1[CH2:7][O:8][C:9]1[CH:18]=[C:17]2[C:12]([CH2:13][CH2:14][C:15](=[O:19])[N:16]2[CH2:33][C:34]([OH:36])=[O:35])=[CH:11][CH:10]=1

Participants

8

Reactant 4

HCID 6422Trifluoroacetic acidHCID 24758Sodium hydrideHCID 79177tert-Butyl bromoacetateHCID 576754887-[4-Methyl-2-(4-trifluoromethyl-phenyl)-thiazol-5-ylmethoxy]-3,4-dihydro-1H-quinolin-2-one

Product 1

HCID 10344905{7-[4-Methyl-2-(4-trifluoromethyl-phenyl)-thiazol-5-ylmethoxy]-2-oxo-3,4-dihydro-2H-quinolin-1-yl}-acetic acidYield 25%

Reagents, catalysts & solvents 3

HCID 962WaterSolventHCID 6228DimethylformamideSolventHCID 6344DichloromethaneSolvent

Conditions

Temperature
57 °C

Procedure

A solution of 7-[4-methyl-2-(4-trifluoromethyl-phenyl)-thiazol-5-ylmethoxy]-3,4-dihydro-1H-quinolin-2-one (233 mg, 0.557 mmol) in DMF (3.0 mL) is treated with NaH (67 mg, 1.67 mmol, 60%). The resulting suspension is heated at 57° C. for 40 minutes and cooled to room temperature. The t-butyl bromoacetate (217 mg, 1.11 mmol) is added and the suspension is stirred for 2 hours and then quenched with water. The mixture is extracted with EtOAc (30 mL×2) and the combined organics are dried (Na2SO4), concentrated, and purified on silica gel chromatography column with 20% EtOAc/Hexanes to obtain the intermediate compound. The intermediate is then treated with TFA (1.0 ml), CH2Cl2 (1.0 ml), H2O (0.1 mL) and stirred for 2 hours, concentrated and purified on silica gel chromatography (Hexanes/EtOAc/HOAc, 5/5/0.02) afford the title compound (65 mg, 25%). MS (MH+): 477.1; the structure is also confirmed by proton NMR.

Workup

  1. temperaturecooled to room temperature
  2. customquenched with water
  3. extractionThe mixture is extracted with EtOAc (30 mL×2)
  4. dry with materialthe combined organics are dried (Na2SO4)
  5. concentrationconcentrated
  6. custompurified on silica gel chromatography column with 20% EtOAc/Hexanes
  7. customto obtain the intermediate compound
  8. stirringstirred for 2 hours
  9. concentrationconcentrated
  10. custompurified on silica gel chromatography (Hexanes/EtOAc/HOAc, 5/5/0.02)

Sources & evidence

ORD record
ord-beb075b825a447ecbbe061259b4604a8
Source dataset
uspto-grants-2009_05
Patent number
US07528160B2

Reaction notes

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