Methyl iodide → HCID 66607450, compound

HRID 563503Notes

Reaction equation

HRID 563503 reaction equation
[CH2:1]([O:3][C:4](=[O:31])[CH2:5][C:6]1[CH:7]=[C:8]([C:14]2[CH:19]=[CH:18][C:17]([C:20]([F:23])([F:22])[F:21])=[CH:16][C:15]=2[CH2:24][N:25]([C:28](=[O:30])[CH3:29])[CH2:26][CH3:27])[C:9]([O:12][CH3:13])=[CH:10][CH:11]=1)[CH3:2].IC.[CH3:34][Si](C)(C)[N-][Si](C)(C)C.[Na+]>C1COCC1>[CH2:1]([O:3][C:4](=[O:31])[CH:5]([C:6]1[CH:7]=[C:8]([C:14]2[CH:19]=[CH:18][C:17]([C:20]([F:22])([F:23])[F:21])=[CH:16][C:15]=2[CH2:24][N:25]([C:28](=[O:30])[CH3:29])[CH2:26][CH3:27])[C:9]([O:12][CH3:13])=[CH:10][CH:11]=1)[CH3:34])[CH3:2]

Participants

5

Reactant 3

HCID 6328Methyl iodideHCID 2724254Sodium bis(trimethylsilyl)amideHCID 66607706HCID 66607706, compound

Product 1

HCID 66607450HCID 66607450, compound

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Conditions

Temperature
-78 °C

Procedure

{2′-[(Acetyl-ethyl-amino)-methyl]-6-methoxy-4′-trifluoromethyl-biphenyl-3-yl}-acetic acid ethyl ester (0.143 g, 0.33 mmol) and iodomethane (0.02 mL, 0.36 mmol) were combined in THF (1.5 mL) and cooled to −78° C. Sodium hexamethyldisilazide (1 M in THF; 0.36 mL, 0.36 mmol) was added, and the mixture was stirred for 1 hour at −78° C. Once no starting material was seen by analytical LCMS, the mixture was quenched with aqueous 1N HCl and diluted with CH2Cl2. The aqueous layer was separated and extracted with CH2Cl2, and the combined organic layers were washed with H2O, dried over MgSO4, filtered, and concentrated. The residue was purified by silica gel chromatography (0-100% EtOAc in hexanes) to give the title compound.

Workup

  1. customthe mixture was quenched with aqueous 1N HCl
  2. additiondiluted with CH2Cl2
  3. customThe aqueous layer was separated
  4. extractionextracted with CH2Cl2
  5. washthe combined organic layers were washed with H2O
  6. dry with materialdried over MgSO4
  7. filtrationfiltered
  8. concentrationconcentrated
  9. customThe residue was purified by silica gel chromatography (0-100% EtOAc in hexanes)

Sources & evidence

ORD record
ord-12bc31146b014df08ce541391e0bcac1
Source dataset
uspto-grants-2011_11
Patent number
US08067445B2

Reaction notes

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