Trimethylsilylacetylene → HCID 67981331, compound

HRID 1520022Notes

Reaction equation

HRID 1520022 reaction equation
[CH3:1][Si:2]([C:5]#[CH:6])([CH3:4])[CH3:3].Br[C:8]1[C:16]2[C:11](=[CH:12][CH:13]=[C:14]([CH2:17][OH:18])[CH:15]=2)[N:10]([C:19]([O:21][C:22]([CH3:25])([CH3:24])[CH3:23])=[O:20])[N:9]=1>CC([O-])=O.CC([O-])=O.[Pd+2].[Cu](I)I.C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1>[OH:18][CH2:17][C:14]1[CH:15]=[C:16]2[C:11](=[CH:12][CH:13]=1)[N:10]([C:19]([O:21][C:22]([CH3:25])([CH3:24])[CH3:23])=[O:20])[N:9]=[C:8]2[C:6]#[C:5][Si:2]([CH3:4])([CH3:3])[CH3:1]

Participants

6

Reactant 2

HCID 66111TrimethylsilylacetyleneHCID 67981017HCID 67981017, compound

Product 1

HCID 67981331HCID 67981331, compoundYield 137.2%

Reagents, catalysts & solvents 3

HCID 11776TriphenylphosphineCatalystHCID 83717Copper iodideCatalystHCID 167845palladium(II) acetateCatalyst

Procedure

A mixture of trimethylsilylacetylene (1.60 mL; 11.3 mmol; 2.1 eq.), tert-butyl 3-bromo-5-(hydroxymethyl)-1H-indazole-1-carboxylate (1.80 g; 5.50 mmol; 1.0 eq.), Pd(OAc)2 (54 mg; 0.24 mmol; 0.04 eq.), triphenylphosphine (115 mg; 0.44 mmol; 0.08 eq.) and Copper iodide (62 mg; 0.33 mmol; 0.06 eq.) in TEA (50 mL) was degassed then heated at reflux for 3 h. After cooling, it was poured into HCl (0.1 N solution) and extracted with EtOAc. Combined organic phases were washed with brine, dried over magnesium sulfate, filtered and concentrated to give the title compound as a brown oil (2.6 g). 1H NMR (300 MHz, DMSO-d6) δ 8.06 (d, J=8.7 Hz, 1H), 7.71 (s, 1H), 7.60 (dd, J=1.6, 8.7 Hz, 1H), 5.41 (t, J=5.7 Hz, 1H), 4.66 (d, J=5.7 Hz, 2H), 1.65 (s, 9H), 0.32 (s, 9H). MS (ESI+): 345.2.

Workup

  1. customwas degassed
  2. temperaturethen heated
  3. temperatureat reflux for 3 h
  4. temperatureAfter cooling
  5. additionit was poured into HCl (0.1 N solution)
  6. extractionextracted with EtOAc
  7. washCombined organic phases were washed with brine
  8. dry with materialdried over magnesium sulfate
  9. filtrationfiltered
  10. concentrationconcentrated

Sources & evidence

ORD record
ord-7bf824ad92be4cbfbaa40c6132213b31
Source dataset
uspto-grants-2015_07
Patent number
US09073892B2

Reaction notes

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