HCID 57546020, compound → HCID 57546237, compound

HRID 913891Notes

Reaction equation

HRID 913891 reaction equation
[CH3:1][Mg]Br.[F:4][C:5]([F:26])([F:25])[C:6]1[CH:7]=[C:8]2[C:12](=[C:13]([CH:15]=[O:16])[CH:14]=1)[N:11]([CH2:17][O:18][CH2:19][CH2:20][Si:21]([CH3:24])([CH3:23])[CH3:22])[CH:10]=[CH:9]2>O1CCCC1>[F:26][C:5]([F:4])([F:25])[C:6]1[CH:7]=[C:8]2[C:12](=[C:13]([CH:15]([OH:16])[CH3:1])[CH:14]=1)[N:11]([CH2:17][O:18][CH2:19][CH2:20][Si:21]([CH3:22])([CH3:23])[CH3:24])[CH:10]=[CH:9]2

Participants

4

Reactant 2

HCID 57546020HCID 57546020, compoundHCID 178418573HCID 178418573, compound2×

Product 1

HCID 57546237HCID 57546237, compound

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Conditions

Temperature
0 °C

Procedure

Methylmagnesium bromide (0.582 ml, 1.747 mmol) was added dropwise to a 0° C. solution of 5-(trifluoromethyl)-1-((2-(trimethylsilyl)ethoxy)methyl)-1H-indole-7-carbaldehyde (500 mg, 1.456 mmol) in tetrahydrofuran (10 ml). The reaction was stirred 30 min at 0° C. An additional portion of methylmagnesium bromide (0.58 ml, 1.75 mmol) was added. The reaction was stirred another 30 min, quenched by addition of water (10 mL), and extracted with ethyl acetate (3×10 ml). The combined organic layers were dried with magnesium sulfate and evaporated. The residue was purified by chromatography on silica gel with a gradient of 5% to 40% ethyl acetate/hexanes to give 427 mg (82%) as a yellow liquid. 1H-NMR (CDCl3, 400 MHz) δ 7.84 (d, J=1.1 Hz, 1H), 7.62 (d, J=1.0 Hz, 1H), 7.18 (d, J=3.2 Hz, 1H), 6.59 (d, J=3.3 Hz, 1H), 5.74 (d, J=11.5 Hz, 1H), 5.68 (m, 1H), 5.59 (d, J=11.4 Hz, 1H), 3.44 (dd, J=8.4, 7.8 Hz, 2H), 1.69 (d, J=6.3 Hz, 3H), 0.87 (m, 2H), −0.10 (s, 9H); LC/MS (HPLC method 4): tR=3.743 min, 382.12(MH)+.

Workup

  1. stirringThe reaction was stirred another 30 min
  2. customquenched by addition of water (10 mL)
  3. extractionextracted with ethyl acetate (3×10 ml)
  4. dry with materialThe combined organic layers were dried with magnesium sulfate
  5. customevaporated
  6. customThe residue was purified by chromatography on silica gel with a gradient of 5% to 40% ethyl acetate/hexanes
  7. customto give 427 mg (82%) as a yellow liquid

Sources & evidence

ORD record
ord-b32a99e76ed643d8abaa44d6dff63689
Source dataset
uspto-grants-2011_09
Patent number
US08026257B2

Reaction notes

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