Triisopropyl borate → HCID 67974323, compound

HRID 1502456Notes

Reaction equation

HRID 1502456 reaction equation
Br[C:2]1[C:3]([CH3:21])=[CH:4][C:5]([CH:8]([O:13][Si:14]([C:17]([CH3:20])([CH3:19])[CH3:18])([CH3:16])[CH3:15])[C:9]([F:12])([F:11])[F:10])=[N:6][CH:7]=1.[B:22](OC(C)C)([O:27]C(C)C)[O:23]C(C)C>C1COCC1>[Si:14]([O:13][CH:8]([C:5]1[N:6]=[CH:7][C:2]([B:22]([OH:27])[OH:23])=[C:3]([CH3:21])[CH:4]=1)[C:9]([F:12])([F:11])[F:10])([C:17]([CH3:20])([CH3:19])[CH3:18])([CH3:16])[CH3:15]

Participants

4

Reactant 2

HCID 21531Triisopropyl borateHCID 71115027HCID 71115027, compound

Product 1

HCID 67974323HCID 67974323, compoundYield 37%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent2×

Conditions

Temperature
-78 °C

Procedure

Isopropylmagnesium chloride lithium chloride complex (1.3 mol/L) in THF (0.72 mL, 0.94 mmol) was added to a solution of 5-bromo-2-(1-(tert-butyldimethylsilyloxy)-2,2,2-trifluoroethyl)-4-methylpyridine (120 mg, 0.312 mmol) in THF (1 mL) cooled at −78° C. The reaction mixture was warmed to room temperature and stirred for 1 hour. The mixture was then cooled at −78° C. and triisopropyl borate (0.26 ml, 1.09 mmol) was added. After 5 minutes, the reaction mixture was warmed to room temperature. After 1 hour at room temperature, the reaction was quenched with a few drops of saturated aqueous ammonium chloride solution. The reaction mixture was diluted with ethyl acetate (15 mL) and washed with water (5 ml). The organic layer was separated, dried over sodium sulfate, filtered and concentrated in vacuo to provide a residue that was purified by flash chromatography (4 g, silica, 0-10% methanol in dichloromethane). Desired fractions were combined and evaporated in vacuo to afford the title compound as a white solid (40 mg, 37%), which was used in the next step without further purification.

Workup

  1. temperatureThe reaction mixture was warmed to room temperature
  2. temperatureThe mixture was then cooled at −78° C.
  3. waitAfter 5 minutes
  4. temperaturethe reaction mixture was warmed to room temperature
  5. waitAfter 1 hour at room temperature
  6. customthe reaction was quenched with a few drops of saturated aqueous ammonium chloride solution
  7. additionThe reaction mixture was diluted with ethyl acetate (15 mL)
  8. washwashed with water (5 ml)
  9. customThe organic layer was separated
  10. dry with materialdried over sodium sulfate
  11. filtrationfiltered
  12. concentrationconcentrated in vacuo
  13. customto provide a residue that
  14. customwas purified by flash chromatography (4 g, silica, 0-10% methanol in dichloromethane)
  15. customevaporated in vacuo

Sources & evidence

ORD record
ord-cf8233a8fcf74e97b0aff2ab54125c5a
Source dataset
uspto-grants-2015_12
Patent number
US09206175B2

Reaction notes

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