Potassium Phosphate, Tribasic → 4-Cyclopropyl-2-hydroxybenzonitrile

HRID 80761

Reaction equation

HRID 80761 reaction equation
Br[C:2]1[CH:9]=[CH:8][C:5]([C:6]#[N:7])=[C:4]([OH:10])[CH:3]=1.[CH:11]1([B-](F)(F)F)[CH2:13][CH2:12]1.[K+].[O-]P([O-])([O-])=O.[K+].[K+].[K+]>C1(C)C=CC=CC=1.CCOC(C)=O.[NH4+].[Cl-].CC(P(C(C)(C)C)C1C=CC(N(C)C)=CC=1)(C)C.CC(P(C(C)(C)C)C1C=CC(N(C)C)=CC=1)(C)C.Cl[Pd]Cl>[CH:11]1([C:2]2[CH:9]=[CH:8][C:5]([C:6]#[N:7])=[C:4]([OH:10])[CH:3]=2)[CH2:13][CH2:12]1

Participants

7

Reactant 3

HCID 62657Potassium Phosphate, TribasicHCID 129669614-Bromo-2-hydroxybenzonitrileHCID 23697338Potassium cyclopropyltrifluoroborate

Product 1

HCID 866902504-Cyclopropyl-2-hydroxybenzonitrile

Reagents, catalysts & solvents 3

HCID 11714597Bis(di-tert-butyl(4-dimethylaminophenyl)phosphine)dichloropalladium(II)CatalystHCID 1140TolueneSolventHCID 86583716Ammonium chloride ethyl acetateSolvent

Conditions

Temperature
100 °C

Procedure

A solution of 4-bromo-2-hydroxybenzonitrile (1 g, 5.05 mmol), potassium cyclopropyltrifluoroborate (1.495 g, 10.10 mmol), K3PO4 (5.05 ml, 15.15 mmol) and PdCl2(Amphos)2 (0.358 g, 0.505 mmol) in toluene (25 mL) was allowed to stir at 100° C. under nitrogen overnight. The mixture was then cooled to room temperature, diluted with EtOAc/NH4Cl(aq), and filtered through a pad of Celite. The organic layer was seperated, dried over Na2SO4, filtered and concentrated. The residue was purified by FCC (0-50% EtOAc/heptane) to provide 4-cyclopropyl-2-hydroxybenzonitrile, 1H NMR (400 MHz, CH2Cl2) δ 12.17 (br. s., 1H), 7.23 (d, J=8.34 Hz, 1H), 6.51-6.58 (m, 2H), 1.82 (tt, J=5.02, 8.37 Hz, 1H), 0.94-1.00 (m, 2H), 0.68-0.73 (m, 2H).

Workup

  1. temperatureThe mixture was then cooled to room temperature
  2. filtrationfiltered through a pad of Celite
  3. customThe organic layer was seperated
  4. dry with materialdried over Na2SO4
  5. filtrationfiltered
  6. concentrationconcentrated
  7. customThe residue was purified by FCC (0-50% EtOAc/heptane)

Sources & evidence

ORD record
ord-4c162c32089e4416946d0dfff84ac7b6
Source dataset
uspto-grants-2014_09
Patent number
US08846656B2

Linked notes

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