Trimethyl borate → HCID 67410628, compound

HRID 909158Notes

Reaction equation

HRID 909158 reaction equation
Br[C:2]1[CH:3]=[C:4]2[C:8](=[CH:9][CH:10]=1)[N:7]([CH2:11][CH2:12][CH2:13][O:14][Si:15]([C:28]([CH3:31])([CH3:30])[CH3:29])([C:22]1[CH:27]=[CH:26][CH:25]=[CH:24][CH:23]=1)[C:16]1[CH:21]=[CH:20][CH:19]=[CH:18][CH:17]=1)[N:6]=[CH:5]2.C([Li])CCC.[B:37](OC)([O:40]C)[O:38]C>C1COCC1>[Si:15]([O:14][CH2:13][CH2:12][CH2:11][N:7]1[C:8]2[C:4](=[CH:3][C:2]([B:37]([OH:40])[OH:38])=[CH:10][CH:9]=2)[CH:5]=[N:6]1)([C:28]([CH3:31])([CH3:29])[CH3:30])([C:22]1[CH:27]=[CH:26][CH:25]=[CH:24][CH:23]=1)[C:16]1[CH:21]=[CH:20][CH:19]=[CH:18][CH:17]=1

Participants

5

Reactant 3

HCID 8470Trimethyl borateHCID 67409251HCID 67409251, compoundHCID 178418339Butyllithium

Product 1

HCID 67410628HCID 67410628, compoundYield 52%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Conditions

Temperature
-78 °C

Procedure

5-Bromo-1-[3-(tert-butyl-diphenylsilanyloxy)-propyl]-1H-indazole (3 s) (200 mg, 0.41 mmol) was dissolved in 4.0 mL THF and cooled to −78° C. A solution of n-butyl lithium in hexanes (2.5M, 0.17 mL) was added slowly. The yellow solution was stirred for 30 minutes. Trimethyl borate (130 mg, 1.2 mmol) was added and the reaction was warmed to room temperature and stirred for 30 min. The reaction was quenched with 10 mL of a 0.3% aqueous HCl solution and the resulting mixture was stirred for 30 min. The reaction was diluted with Et2O and the layers were separated. The organic phase was washed with brine. The aqueous phases were extracted once with Et2O. The organic phases were combined, dried (MgSO4), filtered, and concentrated in vacuo. The crude product was partially purified on silica gel with 3% MeOH/CH2Cl2 to afford (4s) (97 mg, 52%). MS (ESI+) m/z 459 (M+H)+. HPLC (5 to 95%) 3.74 min. This mixture was carried on to the next step without further purification.

Workup

  1. temperaturethe reaction was warmed to room temperature
  2. stirringstirred for 30 min
  3. customThe reaction was quenched with 10 mL of a 0.3% aqueous HCl solution
  4. stirringthe resulting mixture was stirred for 30 min
  5. additionThe reaction was diluted with Et2O
  6. customthe layers were separated
  7. washThe organic phase was washed with brine
  8. extractionThe aqueous phases were extracted once with Et2O
  9. dry with materialdried (MgSO4)
  10. filtrationfiltered
  11. concentrationconcentrated in vacuo
  12. customThe crude product was partially purified on silica gel with 3% MeOH/CH2Cl2

Sources & evidence

ORD record
ord-cccddca5dc8142df8b993a6cfd462d75
Source dataset
uspto-grants-2011_09
Patent number
US08017641B2

Reaction notes

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