5-Chloro-2-((2-(trimethylsilyl)ethoxy)methyl)-2H-indazole-7-carbaldehyde → (+/-)-1-(5-Chloro-2-((2-(trimethylsilyl)ethoxy)methyl)-2H-indazol-7-yl)ethanol

HRID 913830Notes

Reaction equation

HRID 913830 reaction equation
[Cl:1][C:2]1[CH:10]=[C:9]([CH:11]=[O:12])[C:8]2[C:4](=[CH:5][N:6]([CH2:13][O:14][CH2:15][CH2:16][Si:17]([CH3:20])([CH3:19])[CH3:18])[N:7]=2)[CH:3]=1.[CH3:21][Mg]Br>O1CCCC1>[Cl:1][C:2]1[CH:10]=[C:9]([CH:11]([OH:12])[CH3:21])[C:8]2[C:4](=[CH:5][N:6]([CH2:13][O:14][CH2:15][CH2:16][Si:17]([CH3:20])([CH3:19])[CH3:18])[N:7]=2)[CH:3]=1

Participants

4

Reactant 2

HCID 575462315-Chloro-2-((2-(trimethylsilyl)ethoxy)methyl)-2H-indazole-7-carbaldehydeHCID 178418573HCID 178418573, compound

Product 1

HCID 57545985(+/-)-1-(5-Chloro-2-((2-(trimethylsilyl)ethoxy)methyl)-2H-indazol-7-yl)ethanol

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Conditions

Temperature
-78 °C

Procedure

5-Chloro-2-((2-(trimethylsilyl)ethoxy)methyl)-2H-indazole-7-carbaldehyde (0.88 g, 2.83 mmol) was dissolved in tetrahydrofuran (10 mL), cooled to −78° C. and treated with methylmagnesium bromide (3.0 M in diethyl ether, 0.9 mL, 2.83 mmol) over several minutes. After 1 h, cooling was removed and stirring continued for 1 h at room temperature. The reaction was cooled to 0° C., treated with saturated ammonium chloride and diluted with ethyl acetate. The layers were separated. The organic layer was washed with water (2×), brine (2×), dried over sodium sulfate, filtered and concentrated. Flash chromatography on silica gel (30% ethyl acetate/hexanes) afforded 540 mg (58%) as a light brown oil. 1H-NMR (CDCl3, 300 MHz) δ 8.00 (s, 1H), 8.21 (s, 1H), 7.50 (d, J=1.8 Hz, 1H), 7.13 (m, 1H), 5.65 (s, 2H), 5.28 (q, J=6.2 Hz, 1H), 3.57-3.62 (m, 2H), 1.64 (d, J=6.2 Hz, 3H), 0.86-0.92 (m, 2H), 0.07 (s, 9H). Mass spec.: 327.04 (MH)+.

Workup

  1. temperaturecooling
  2. customwas removed
  3. waitcontinued for 1 h at room temperature
  4. temperatureThe reaction was cooled to 0° C.
  5. additiontreated with saturated ammonium chloride
  6. additiondiluted with ethyl acetate
  7. customThe layers were separated
  8. washThe organic layer was washed with water (2×), brine (2×)
  9. dry with materialdried over sodium sulfate
  10. filtrationfiltered
  11. concentrationconcentrated
  12. customFlash chromatography on silica gel (30% ethyl acetate/hexanes) afforded 540 mg (58%) as a light brown oil

Sources & evidence

ORD record
ord-241b020f589844ee8847bfbb2cd4fd77
Source dataset
uspto-grants-2011_09
Patent number
US08026257B2

Reaction notes

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