Potassium Carbonate → HCID 90122616, compound

HRID 1480617Notes

Reaction equation

HRID 1480617 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.[F:17][C:18]([F:29])([F:28])[C:19]1[N:24]=[CH:23][C:22](B(O)O)=[CH:21][CH:20]=1.[C:30](=[O:33])([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:22]2[CH:23]=[N:24][C:19]([C:18]([F:29])([F:28])[F:17])=[CH:20][CH:21]=2)[CH:3]=[C:2]([C:15]2[CH:23]=[N:24][C:19]([C:18]([F:29])([F:28])[F:17])=[CH:20][CH:21]=2)[C:30]=1[OH:33])([CH3:12])([CH3:13])[CH3:14]

Participants

7

Reactant 3

HCID 11430Potassium CarbonateHCID 251342782-(Trifluoromethyl)pyridine-5-boronic AcidHCID 86718560HCID 86718560, compound2×

Product 1

HCID 90122616HCID 90122616, compoundYield 42.6%

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), 6-(trifluoromethyl)pyridine-3-boronic acid [purchased from Frontier Scientific] (1.025 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)palladium (0) (114 mg, 0.099 mmol) was added and the resulting mixture heated at 72° C. for 60 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 using flash chromatography on silica eluting with a solvent gradient of 0 to 30% ethyl acetate in hexanes to give a yellow solid. The solid was triturated with 1:1 v/v MTBE/hexane, filtered and then dried at 40° C./4-8 mm Hg to give 2-((tert-butylamino)methyl)-4,6-bis(6-(trifluoromethyl)pyridin-3-yl)phenol (0.358 g) 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
  11. customto give a yellow solid
  12. customThe solid was triturated with 1:1 v/v MTBE/hexane
  13. filtrationfiltered
  14. customdried at 40° C./4-8 mm Hg

Sources & evidence

ORD record
ord-1b062d6300ea448b9c654c59c2504bf5
Source dataset
uspto-grants-2016_08
Patent number
US09409893B2

Reaction notes

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