Sodium hydride → (2-Thiazol-2-yl-4-trifluoromethyl-imidazol-1-yl)-acetic acid methyl ester

HRID 895557Notes

Reaction equation

HRID 895557 reaction equation
[H-].[Na+].[F:3][C:4]([F:16])([F:15])[C:5]1[N:6]=[C:7]([C:10]2[S:11][CH:12]=[CH:13][N:14]=2)[NH:8][CH:9]=1.Br[CH2:18][C:19]([O:21][CH3:22])=[O:20]>C1COCC1.O.[Cl-].[Na+].O>[F:16][C:4]([F:3])([F:15])[C:5]1[N:6]=[C:7]([C:10]2[S:11][CH:12]=[CH:13][N:14]=2)[NH:8][CH:9]=1.[CH3:22][O:21][C:19](=[O:20])[CH2:18][N:8]1[CH:9]=[C:5]([C:4]([F:3])([F:15])[F:16])[N:6]=[C:7]1[C:10]1[S:11][CH:12]=[CH:13][N:14]=1

Participants

8

Reactant 3

HCID 24758Sodium hydrideHCID 60984Methyl bromoacetateHCID 178506253HCID 178506253, compound

Product 2

HCID 68499036(2-Thiazol-2-yl-4-trifluoromethyl-imidazol-1-yl)-acetic acid methyl esterHCID 178506253HCID 178506253, compound

Reagents, catalysts & solvents 3

HCID 962WaterSolventHCID 8028TetrahydrofuranSolvent2×HCID 57417360Sodium chloride; waterSolvent

Conditions

Temperature
0 °C

Procedure

To a suspension of NaH (109 mg of a 60% dispersion in mineral oil, 2.74 mmol) in THF (10 mL) at 0° C. under N2 is added a solution of 2-(4-trifluoromethyl-1H-imidazol-2-yl)-thiazole (500 mg, 2.28 mmol) in THF (4 mL) via cannula, followed by a 1 mL rinse. The mixture is stirred at 0° C. for 30 min and then treated with methyl bromoacetate (0.28 mL, 2.97 mmol). The reaction mixture is stirred overnight while slowly warming to rt. It is then diluted with H2O (10 mL) and the resulting mixture stirred vigorously for 5 min. The mixture is further diluted with some brine and then extracted twice with EtOAc. The combined extracts are dried over Na2SO4 and concentrated. The crude material is purified by flash chromatography on silica gel. Elution with 4:1 hexanes-EtOAc followed by 3:1 hexanes-EtOAc affords unreacted 2-(4-trifluoromethyl-1H-imidazol-2-yl)-thiazole as well as (2-thiazol-2-yl-4-trifluoromethyl-imidazol-1-yl)-acetic acid methyl ester. 1H NMR (CDCl3, 400 MHz) δ 7.82 (d, J=3.2 Hz, 1H), 7.40 (d, J=3.2 Hz, 1H), 7.35 (s, 1H), 5.41 (s, 2H), 3.77 (s, 3H) ppm.

Workup

  1. washrinse
  2. stirringThe reaction mixture is stirred overnight
  3. temperaturewhile slowly warming to rt
  4. stirringthe resulting mixture stirred vigorously for 5 min
  5. extractionextracted twice with EtOAc
  6. dry with materialThe combined extracts are dried over Na2SO4
  7. concentrationconcentrated
  8. customThe crude material is purified by flash chromatography on silica gel
  9. washElution with 4:1 hexanes-EtOAc

Sources & evidence

ORD record
ord-c33f71709ed94a2f87adc841f45aa390
Source dataset
uspto-grants-2005_07
Patent number
US06916819B2

Reaction notes

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