Dichloromethane → 3-(4-Hydroxyphenyl)benzonitrile

HRID 1597413Notes

Reaction equation

HRID 1597413 reaction equation
C(Cl)Cl.I[C:5]1[CH:6]=[C:7]([CH:10]=[CH:11][CH:12]=1)[C:8]#[N:9].C[O:14][C:15]1[CH:20]=[CH:19][C:18](B(O)O)=[CH:17][CH:16]=1.[F-].[Cs+]>C1C=CC(P(C2C=CC=CC=2)[C-]2C=CC=C2)=CC=1.C1C=CC(P(C2C=CC=CC=2)[C-]2C=CC=C2)=CC=1.Cl[Pd]Cl.[Fe+2].COCCOC>[C:8]([C:7]1[CH:6]=[C:5]([C:18]2[CH:19]=[CH:20][C:15]([OH:14])=[CH:16][CH:17]=2)[CH:12]=[CH:11][CH:10]=1)#[N:9]

Participants

7

Reactant 4

HCID 6344DichloromethaneHCID 25953Cesium fluorideHCID 1443413-IodobenzonitrileHCID 201262(4-Methoxyphenyl)boronic acid

Product 1

HCID 37790963-(4-Hydroxyphenyl)benzonitrileYield 619.2%

Reagents, catalysts & solvents 2

HCID 178418228Bis(cyclopenta-1,4-dien-1-yl(diphenyl)phosphane);dichloropalladium;iron(2+)CatalystHCID 80711,2-DimethoxyethaneSolvent

Procedure

A 250 mL flask was charged with 2.21 g (2.7 mmol) [1,1′-Bis(diphenylphosphino)ferrocene]dichloropalladium (II).CH2Cl2 and 6.26 g (2.73 mmol) 3-iodobenzonitrile, 6.0 g (3.95 mmol) 4-methoxyphenylboronic acid and 12.45 g (8.20 mmol) cesium fluoride added as solids followed by addition of 180 mL 1,2-dimethoxyethane. The flask was flushed with N2 and the suspension heated to reflux which was maintained for 3 hours. the cooled reaction mixture was filtered through a pad of 300 g flash silica gel and the pad was washed with 1 L ethyl acetate. The ethyl acetate was concentrated and the residue purified by flash chromatography eluting with 10% hexanes/90% ethyl acetate to give 3.3 g of the desired product (58% yield). This material was dissolved in 50 mL anhydrous CH2Cl2 and the solution cooled in a dry ice-acetone bath and a solution of boron tribromide (40 mL, 4 mmol) was added dropwise under inert atmosphere. The reaction solution was then stirred at room temperature overnight. The reaction solution was cooled in an ice bath and 5 mL of H2O added dropwise followed by the addition of 20 mL 1N HCl. The mixture was stirred for 1 hour and the resulting suspension was filtered and the filtrate transferred to a separatory funnel and the organic layer separated off and set aside. the filtered solid was washed with H2O and ethyl acetate and filtered and the filtrate transferred to the separatory funnel and the organic layer combined with the previous organic layer, dried over Na2SO4, filtered and the filtrate concentrated to a 3.05 g of a white solid (99% yield).

Workup

  1. customThe flask was flushed with N2
  2. temperaturethe suspension heated
  3. temperatureto reflux which
  4. temperaturewas maintained for 3 hours
  5. customthe cooled reaction mixture
  6. filtrationwas filtered through a pad of 300 g flash silica gel
  7. washthe pad was washed with 1 L ethyl acetate
  8. concentrationThe ethyl acetate was concentrated
  9. customthe residue purified by flash chromatography
  10. washeluting with 10% hexanes/90% ethyl acetate

Sources & evidence

ORD record
ord-dee8a7077f564e9bafe02b2c0dc1f9e8
Source dataset
uspto-grants-2001_09
Patent number
US06294573B1

Reaction notes

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