Benzyl Bromide → HCID 89648997, compound

HRID 1773982Notes

Reaction equation

HRID 1773982 reaction equation
Br[C:2]1[CH:7]=[CH:6][C:5]([OH:8])=[C:4]([CH:9]([CH3:11])[CH3:10])[CH:3]=1.[H-].[Na+].[CH2:14](Br)[C:15]1[CH:20]=[CH:19][CH:18]=[CH:17][CH:16]=1.[Cl-].[C:23]([O:27][C:28](=[O:31])[CH2:29][Zn+])([CH3:26])([CH3:25])[CH3:24]>CN(C=O)C.O1CCOCC1.CC(C)([P](C(C)(C)C)([Pd][P](C(C)(C)C)(C(C)(C)C)C(C)(C)C)C(C)(C)C)C.O.CCOC(C)=O>[C:23]([O:27][C:28](=[O:31])[CH2:29][C:2]1[CH:7]=[CH:6][C:5]([O:8][CH2:14][C:15]2[CH:20]=[CH:19][CH:18]=[CH:17][CH:16]=2)=[C:4]([CH:9]([CH3:11])[CH3:10])[CH:3]=1)([CH3:26])([CH3:25])[CH3:24]

Participants

10

Reactant 4

HCID 7498Benzyl BromideHCID 24758Sodium hydrideHCID 147934824-Bromo-2-(propan-2-yl)phenolHCID 178451183HCID 178451183, compound

Product 1

HCID 89648997HCID 89648997, compound

Reagents, catalysts & solvents 5

HCID 178418851HCID 178418851, compoundCatalystHCID 962WaterSolventHCID 6228DimethylformamideSolventHCID 8857Ethyl AcetateSolventHCID 312751,4-DioxaneSolvent

Procedure

A solution of 4-bromo-2-isopropyl-phenol (1.98 g, 9.1 mmol, 1.0 eq.) in DMF (27 mL) was slowly added to sodium hydride 60% dispersion in mineral oil (476 mg, 11.9 mmol, 1.3 eq.) at 0° C. under N2. Upon completion of the addition, the mixture was allowed to warm to r.t. Benzyl bromide (1.1 mL, 9.1 mmol, 1.0 eq.) was added and the resulting mixture was stirred at r.t. for 18 hours. AcOEt was added and the reaction was stirred for 30 min. Water was added to the mixture. The layers were separated and the org. phase was washed with water and sat. aq. NaCl soln., dried over MgSO4, filtered, and concentrated in vacuo. To a solution of the residue in dioxane (75 mL), a solution of 2-tert-butoxy-2-oxoethylzinc chloride (33.9 mL, 17 mmol, 1.8 eq.) and bis(tri-tert-butylphosphine)palladium(0) (739 mg, 1.42 mmol, 0.15 eq) were added. The resulting mixture was stirred at r.t. for 18 hours. The mixture was filtered through Celite and the filter cake was rinsed with dioxane. The filtrate was concentrated in vacuo. The residue was purified by flashmaster (column: 100 g, flow: 45 mL/min, 30 fractions of 45 mL, Heptane 100% to Heptane+12% AcOEt) to yield (4-benzyloxy-3-isopropyl-phenyl)-acetic acid tert-butyl ester as a colorless oil.

Workup

  1. additionUpon completion of the addition
  2. stirringthe reaction was stirred for 30 min
  3. customThe layers were separated
  4. washphase was washed with water and sat. aq. NaCl soln
  5. dry with material, dried over MgSO4
  6. filtrationfiltered
  7. concentrationconcentrated in vacuo
  8. stirringThe resulting mixture was stirred at r.t. for 18 hours
  9. filtrationThe mixture was filtered through Celite
  10. washthe filter cake was rinsed with dioxane
  11. concentrationThe filtrate was concentrated in vacuo
  12. customThe residue was purified by flashmaster (column: 100 g, flow: 45 mL/min, 30 fractions of 45 mL, Heptane 100% to Heptane+12% AcOEt)

Sources & evidence

ORD record
ord-26c1df4ea64c400db48a379909c2398a
Source dataset
uspto-grants-2016_02
Patent number
US09255090B2

Reaction notes

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