HCID 23113986, compound → HCID 23113999, compound

HRID 1787310Notes

Reaction equation

HRID 1787310 reaction equation
[CH3:1][Mg]Br.[CH:4]([C:6]1[C:14]2[S:13][CH2:12][CH:11]([C:15]3[CH:20]=[CH:19][C:18]([CH:21]([CH3:23])[CH3:22])=[CH:17][CH:16]=3)[C:10]=2[C:9]([CH3:24])=[C:8]([NH:25][C:26](=[O:32])[CH2:27][C:28]([CH3:31])([CH3:30])[CH3:29])[C:7]=1[CH3:33])=O>O>[CH2:4]([C:6]1[C:14]2[S:13][CH2:12][CH:11]([C:15]3[CH:16]=[CH:17][C:18]([CH:21]([CH3:22])[CH3:23])=[CH:19][CH:20]=3)[C:10]=2[C:9]([CH3:24])=[C:8]([NH:25][C:26](=[O:32])[CH2:27][C:28]([CH3:30])([CH3:29])[CH3:31])[C:7]=1[CH3:33])[CH3:1]

Participants

4

Reactant 2

HCID 23113986HCID 23113986, compoundHCID 178418573HCID 178418573, compound

Product 1

HCID 23113999HCID 23113999, compoundYield 57.3%

Reagents, catalysts & solvents 1

HCID 962WaterSolvent

Procedure

To methylmagnesium bromide (1.0 M, THF solution, 10 mL, 10 mmol) was added at 0° C. N-(7-formyl-3-(4-isopropylphenyl)-4,6-dimethyl-2,3-dihydro-1-benzothien-5-yl)-3,3-dimethylbutanamide (600 mg, 1.42 mmol) obtained in Example 163 and the reaction solution was stirred at room temperature for 1 hour. The reaction solution was added to water and the product was extracted with ethyl acetate. The organic layer was washed with 1 N hydrochloric acid and saturated brine, dried over anhydrous sodium sulfate, and concentrated under reduced pressure. To a mixture of the obtained residue in trifluoroacetic acid (3 mL) was added with ice-cooling triethylsilane (1.0 mL) and the resulting mixture was stirred at room temperature for 30 minutes. After the reaction solution was concentrated under reduced pressure, to the residue was added an aqueous saturated sodium hydrogen carbonate solution and the aqueous layer was made alkaline, and the mixture was extracted with ethyl acetate. The organic layer was washed with water and saturated brine, dried over anhydrous sodium sulfate, and concentrated under reduced pressure. The obtained residue was purified by silica gel column chromatography (ethyl acetate:hexane=1:4) to obtain 345 mg (yield: 57%) of the title compound. Melting point: 172-173° C. (hexane-ethyl acetate).

Workup

  1. extractionthe product was extracted with ethyl acetate
  2. washThe organic layer was washed with 1 N hydrochloric acid and saturated brine
  3. dry with materialdried over anhydrous sodium sulfate
  4. concentrationconcentrated under reduced pressure
  5. additionTo a mixture of the obtained residue in trifluoroacetic acid (3 mL)
  6. additionwas added with ice-
  7. temperaturecooling triethylsilane (1.0 mL)
  8. concentrationAfter the reaction solution was concentrated under reduced pressure, to the residue
  9. additionwas added an aqueous saturated sodium hydrogen carbonate solution
  10. extractionthe mixture was extracted with ethyl acetate
  11. washThe organic layer was washed with water and saturated brine
  12. dry with materialdried over anhydrous sodium sulfate
  13. concentrationconcentrated under reduced pressure
  14. customThe obtained residue was purified by silica gel column chromatography (ethyl acetate:hexane=1:4)

Sources & evidence

ORD record
ord-15810e0ecd594a7a8a8ddff38dd1bea0
Source dataset
uspto-grants-2009_03
Patent number
US07507841B2

Reaction notes

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