Ethyl Acetate → HCID 46939950, compound

HRID 1095893Notes

Reaction equation

HRID 1095893 reaction equation
[Cl:1][C:2]1[CH:3]=[C:4]([CH:8]=[CH:9][C:10]=1[CH:11]([CH3:25])[C:12]([C:18]1[CH:23]=[CH:22][N:21]=[C:20]([Cl:24])[CH:19]=1)([OH:17])[C:13]([F:16])([F:15])[F:14])[C:5]([OH:7])=O.C1N=CN(C([N:33]2[CH:37]=[N:36]C=C2)=O)C=1.[C:38]([O:41][CH2:42][CH3:43])(=[O:40])C>>[CH2:42]([O:41][C:38]([C:37]1[N:36]=[C:5]([C:4]2[CH:8]=[CH:9][C:10]([CH:11]([CH3:25])[C:12]([C:18]3[CH:23]=[CH:22][N:21]=[C:20]([Cl:24])[CH:19]=3)([OH:17])[C:13]([F:14])([F:15])[F:16])=[C:2]([Cl:1])[CH:3]=2)[O:7][N:33]=1)=[O:40])[CH3:43]

Participants

4

Reactant 3

HCID 8857Ethyl AcetateHCID 682631,1'-CarbonyldiimidazoleHCID 574212683-Chloro-4-[2-(2-chloro-pyridin-4-yl)-3,3,3-trifluoro-2-hydroxy-1-methyl-propyl]-benzoic acid

Product 1

HCID 46939950HCID 46939950, compound

Conditions

Temperature
0 °C

Procedure

To a solution of 3-chloro-4-[2-(2-chloro-pyridin-4-yl)-3,3,3-trifluoro-2-hydroxy-1-methyl-propyl]-benzoic acid (Example 26, 150 mg, 0.238 mmol) in ethyl acetate (5 mL) at 0° C. was added CDI (68 mg, 0.42 mmol). The mixture was stirred for 30 min. at 0° C. Additional ethyl-2-oxoiminooxamate (55 mg, 0.42 mmol) was added. The reaction mixture was washed with water, sat aq NaHCO3 and brine, dried over MgSO4, filtered and concentrated. The residue yellow waxy solid was dissolved in N,N-dimethylformamid (2 mL) and stirred for 3 h at 90° C. and 2 h at 140° C. The mixture was cooled to room temperature, poured in water (20 mL) and extracted twice with AcOEt. The combined organic phases were washed with brine, dried over MgSO4, filtered and concentrated in vacuo. The residue was purified by flash chromatography (silica gel, heptane/AcOEt 3:1) to give title compound (113 mg) as a white waxy solid. MS (m/e)=490.0 [M+H+].

Workup

  1. washThe reaction mixture was washed with water
  2. dry with materialdried over MgSO4
  3. filtrationfiltered
  4. concentrationconcentrated
  5. dissolutionThe residue yellow waxy solid was dissolved in N,N-dimethylformamid (2 mL)
  6. stirringstirred for 3 h at 90° C. and 2 h at 140° C
  7. temperatureThe mixture was cooled to room temperature
  8. additionpoured in water (20 mL)
  9. extractionextracted twice with AcOEt
  10. washThe combined organic phases were washed with brine
  11. dry with materialdried over MgSO4
  12. filtrationfiltered
  13. concentrationconcentrated in vacuo
  14. customThe residue was purified by flash chromatography (silica gel, heptane/AcOEt 3:1)

Sources & evidence

ORD record
ord-e8e363ae2a6a44e1824937642c79c52a
Source dataset
uspto-grants-2012_03
Patent number
US08138189B2

Reaction notes

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