Potassium Carbonate → HCID 86718574, compound

HRID 1480616Notes

Reaction equation

HRID 1480616 reaction equation
Br[C:2]1[CH:3]=[C:4](Br)[C:5]2OC[N:8]([C:11]([CH3:14])([CH3:13])[CH3:12])[CH2:7][C:6]=2[CH:15]=1.[N:17]1[CH:22]=[CH:21][CH:20]=[C:19](B(O)O)[CH:18]=1.[C:26](=[O:29])([O-])[O-].[K+].[K+]>CC(O)C.O.C1C=CC([P]([Pd]([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)[P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)=CC=1>[C:11]([NH:8][CH2:7][C:6]1[CH:5]=[C:4]([C:19]2[CH:18]=[N:17][CH:22]=[CH:21][CH:20]=2)[CH:3]=[C:2]([C:15]2[CH:11]=[N:8][CH:7]=[CH:6][CH:5]=2)[C:26]=1[OH:29])([CH3:12])([CH3:13])[CH3:14]

Participants

7

Reactant 3

HCID 11430Potassium CarbonateHCID 27343783-Pyridinylboronic acidHCID 86718560HCID 86718560, compound2×

Product 1

HCID 86718574HCID 86718574, compoundYield 50.6%

Reagents, catalysts & solvents 3

HCID 178418397HCID 178418397, compoundCatalystHCID 962WaterSolventHCID 3776IsopropanolSolvent

Conditions

Temperature
72 °C

Procedure

A mixture of 6,8-dibromo-3-(tert-butyl)-3,4-dihydro-2H-benzo[e][1,3]oxazine (Intermediate 6) (0.621 g, 1.79 mmol), pyridine-3-boronic acid [purchased from Boron Molecular Limited] (0.660 g, 5.37 mmol) and potassium carbonate (1.979 g, 14.3 mmol) in 2-propanol (30 mL) and water (6 mL) was purged with nitrogen for 20 minutes. Tetrakis(triphenylphosphine)Pd (0) (107 mg, 0.09 mmol) was added and the resulting mixture was heated at 72° C. for 30 minutes then the cooled reaction mixture concentrated under reduced pressure. The residue was dissolved in ethyl acetate, washed with water, dried (MgSO4), filtered and concentrated under reduced pressure to afford a dark brown oil. The product was purified by flash chromatography on silica eluting with a solvent gradient of 0 to 30% ethyl acetate in hexanes to give 2-((tert-butylamino)methyl)-4,6-di(pyridine-3-yl)phenol (151 mg) as an off-white solid.

Workup

  1. customwas purged with nitrogen for 20 minutes
  2. customthe cooled reaction mixture
  3. concentrationconcentrated under reduced pressure
  4. dissolutionThe residue was dissolved in ethyl acetate
  5. washwashed with water
  6. dry with materialdried (MgSO4)
  7. filtrationfiltered
  8. concentrationconcentrated under reduced pressure
  9. customto afford a dark brown oil
  10. customThe product was purified by flash chromatography on silica eluting with a solvent gradient of 0 to 30% ethyl acetate in hexanes

Sources & evidence

ORD record
ord-fb369a0e191244fab8d6438b480deb56
Source dataset
uspto-grants-2016_08
Patent number
US09409893B2

Reaction notes

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