Sodium Iodide → HCID 66699473, compound

HRID 1095934Notes

Reaction equation

HRID 1095934 reaction equation
[Cl:1][C:2]1[CH:3]=[C:4]([OH:23])[CH:5]=[CH:6][C:7]=1[CH:8]([CH3:22])[C:9]([OH:21])([C:14]1[CH:19]=[CH:18][N:17]=[C:16]([CH3:20])[CH:15]=1)[C:10]([F:13])([F:12])[F:11].[H-].[Na+].[CH3:26][O:27][C:28](=[O:37])[CH2:29][N:30]1[CH:34]=[C:33]([CH2:35]Cl)[CH:32]=[N:31]1.[Na+].[I-]>CN(C=O)C>[CH3:26][O:27][C:28](=[O:37])[CH2:29][N:30]1[CH:34]=[C:33]([CH2:35][O:23][C:4]2[CH:5]=[CH:6][C:7]([CH:8]([CH3:22])[C:9]([OH:21])([C:14]3[CH:19]=[CH:18][N:17]=[C:16]([CH3:20])[CH:15]=3)[C:10]([F:13])([F:11])[F:12])=[C:2]([Cl:1])[CH:3]=2)[CH:32]=[N:31]1

Participants

6

Reactant 4

HCID 5238Sodium IodideHCID 24758Sodium hydrideHCID 252541463-Chloro-4-[3,3,3-trifluoro-2-hydroxy-1-methyl-2-(2-methyl-pyridin-4-yl)-propyl]-phenolHCID 66699138HCID 66699138, compound

Product 1

HCID 66699473HCID 66699473, compoundYield 10%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent3×

Conditions

Temperature
0 °C

Procedure

A solution of 3-chloro-4-[3,3,3-trifluoro-2-hydroxy-1-methyl-2-(2-methyl-pyridin-4-yl)-propyl]-phenol (93 mg, obtained in Example 93, step 6) in DMF (2 mL) was added to a suspension of NaH (60% in mineral oil, 24 mg) in DMF (1 mL) over 10 minutes. Stirring was continued for 30 minutes at r.t. The mixture was cooled to 0° C. and (4-chloromethyl-pyrazol-1-yl)-acetic acid methyl ester (61 mg, obtained in Example 103, step 4) dissolved in DMF (2 mL) was added dropwise over a period of 5 minutes. Stirring was continued for 2 hours at r.t. followed by the addition of NaI (3 mg). The mixture was heated to 50° C. overnight. The reaction mixture was cooled, poured into ice and extracted two times with chloroform. The combined organic layers were washed with brine, dried over Na2SO4, filtered and the solvent was evaporated. The residue was purified by flash chromatography (silica gel, gradient of heptane in ethyl acetate) to give the title compound as a light yellow gum (13 mg, 10%). MS (m/e)=498.2 [MH−].

Workup

  1. additionwas added dropwise over a period of 5 minutes
  2. stirringStirring
  3. waitwas continued for 2 hours at r.t.
  4. temperatureThe mixture was heated to 50° C. overnight
  5. temperatureThe reaction mixture was cooled
  6. additionpoured into ice
  7. extractionextracted two times with chloroform
  8. washThe combined organic layers were washed with brine
  9. dry with materialdried over Na2SO4
  10. filtrationfiltered
  11. customthe solvent was evaporated
  12. customThe residue was purified by flash chromatography (silica gel, gradient of heptane in ethyl acetate)

Sources & evidence

ORD record
ord-f7f4628ad5bf4604b5dc6f7fb2cd753a
Source dataset
uspto-grants-2012_03
Patent number
US08138189B2

Reaction notes

Loading…