Cesium carbonate → HCID 86642123, compound

HRID 885916Notes

Reaction equation

HRID 885916 reaction equation
[C:1]([O:5][C:6]([NH:8][C:9]1[CH:14]=[CH:13][C:12]([OH:15])=[CH:11][CH:10]=1)=[O:7])([CH3:4])([CH3:3])[CH3:2].C(=O)([O-])[O-].[Cs+].[Cs+].[CH:22]1(Br)[CH2:25][CH2:24][CH2:23]1>CN(C=O)C>[CH:22]1([O:15][C:12]2[CH:11]=[CH:10][C:9]([NH:8][C:6](=[O:7])[O:5][C:1]([CH3:4])([CH3:2])[CH3:3])=[CH:14][CH:13]=2)[CH2:25][CH2:24][CH2:23]1

Participants

5

Reactant 3

HCID 10796Cesium carbonateHCID 78110BromocyclobutaneHCID 2756771N-Boc-4-hydroxyaniline

Product 1

HCID 86642123HCID 86642123, compoundYield 41%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

To a stirred solution of 4-[N-(tert-butoxycarbonyl)amino]phenol (3.1 g, 14.81 mmol) in DMF (40 mL) was added cesium carbonate (12.1 g, 37.02 mmol) and cyclobutyl bromide (2.0 g, 14.81 mmol). The reaction mixture was stirred at r.t. for 3 days, and then at 60° C. for 19 h. The reaction mixture was cooled to r.t., filtered and partitioned between water (50 mL) and Et2O (100 mL). The layers were separated, and the aqueous fraction was further extracted with Et2O (3×50 mL). The combined organic fractions were washed with brine (50 mL), dried (Na2SO4), filtered and concentrated in vacuo. Purification by column chromatography (SiO2, 5-8% EtOAc/hexanes) gave the title compound (1.6 g, 41%) as a white solid. δH (CDCl3) 7.24 (2H, d, J 8.9 Hz), 6.82-6.72 (2H, m), 6.31 (1H, br. s), 4.67-6.54 (1H, m), 2.52-2.36 (2H, m), 2.25-2.08 (2H, m), 1.94-1.78 (1H, m), 1.77-1.62 (1H, m), 1.53 (9H, s). LCMS (ES+) 208.0 ((M−tBu)+H)+, RT 3.10 minutes (Method 3).

Workup

  1. waitat 60° C. for 19 h
  2. temperatureThe reaction mixture was cooled to r.t.
  3. filtrationfiltered
  4. custompartitioned between water (50 mL) and Et2O (100 mL)
  5. customThe layers were separated
  6. extractionthe aqueous fraction was further extracted with Et2O (3×50 mL)
  7. washThe combined organic fractions were washed with brine (50 mL)
  8. dry with materialdried (Na2SO4)
  9. filtrationfiltered
  10. concentrationconcentrated in vacuo
  11. customPurification by column chromatography (SiO2, 5-8% EtOAc/hexanes)

Sources & evidence

ORD record
ord-bd6c5cd8735840c48ddf3dd6198dd678
Source dataset
uspto-grants-2012_08
Patent number
US08242116B2

Reaction notes

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