tert-Butanol → [3-(2-methyl-1H-imidazol-1-yl)-5-(trifluoromethyl)phenyl]-carbamic acid, 1,1-dimethylethyl ester

HRID 2099453Notes

Reaction equation

HRID 2099453 reaction equation
C([N:3]([CH2:6]C)CC)C.[CH3:8][C:9]1[N:10]([C:14]2[CH:15]=[C:16]([CH:20]=[C:21]([C:23]([F:26])([F:25])[F:24])[CH:22]=2)C(O)=O)[CH:11]=[CH:12][N:13]=1.C1(P(N=[N+]=[N-])(C2C=CC=CC=2)=[O:34])C=CC=CC=1.[C:44]([OH:48])([CH3:47])([CH3:46])[CH3:45]>>[CH3:8][C:9]1[N:10]([C:14]2[CH:15]=[C:16]([NH:3][C:6](=[O:34])[O:48][C:44]([CH3:47])([CH3:46])[CH3:45])[CH:20]=[C:21]([C:23]([F:24])([F:25])[F:26])[CH:22]=2)[CH:11]=[CH:12][N:13]=1

Participants

5

Reactant 4

HCID 6386tert-ButanolHCID 8471TriethylamineHCID 199401P,P-Diphenylphosphinic azideHCID 672143253-(2-Methyl-1H-imidazol-1-yl)-5-(trifluoromethyl)-benzoic acid

Product 1

HCID 86605432[3-(2-methyl-1H-imidazol-1-yl)-5-(trifluoromethyl)phenyl]-carbamic acid, 1,1-dimethylethyl ester

Conditions

Temperature
80 °C

Procedure

Triethylamine (5.23 mL, 37.5 mmol) is added to a stirred suspension of 3-(2-methyl-1H-imidazol-1-yl)-5-(trifluoromethyl)-benzoic acid (Example 91b; 6.8 g, 25 mmol) in t-butanol (200 mL). Diphenylphosphorylazide (7.6 g, 27.5 mmol) is added to the resulting solution and the mixture is heated 80° C. for 16 h. The solvent is evaporated off under reduced pressure and the residue is treated with water (100 mL) and extracted with ethyl acetate (2×100 mL). The combined extracts are washed with brine (100 mL), dried (Na2SO4) and the solvent is evaporated off under reduced pressure to give the crude product which is purified by column chromatography (silica gel, eluent 2% ethanol in ethyl acetate) and recrystallised from ether-hexane to afford the title compound as a colourless crystalline solid, m.p. 203-208° C.

Workup

  1. customThe solvent is evaporated off under reduced pressure
  2. additionthe residue is treated with water (100 mL)
  3. extractionextracted with ethyl acetate (2×100 mL)
  4. washThe combined extracts are washed with brine (100 mL)
  5. dry with materialdried (Na2SO4)
  6. customthe solvent is evaporated off under reduced pressure
  7. customto give the crude product which
  8. customis purified by column chromatography (silica gel, eluent 2% ethanol in ethyl acetate)
  9. customrecrystallised from ether-hexane

Sources & evidence

ORD record
ord-167f5ac2517746bfb0f91ebfe1781e3d
Source dataset
uspto-grants-2009_08
Patent number
US07569566B2

Reaction notes

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