Sulfuric acid magnesium salt (1:1) → 2-Bromo-4-[(4-methoxy-3-methylphenyl)(oxo)acetyl]benzonitrile

HRID 1455134

Reaktionsgleichung

Reaktionsgleichung von HRID 1455134
[Br:1][C:2]1[CH:3]=[C:4]([CH:8]=[CH:9][C:10]=1[C:11]#[N:12])[C:5]([OH:7])=O.[Cl-].[CH3:14][C:15]1[CH:16]=[C:17]([CH:38]=[CH:39][C:40]=1[O:41][CH3:42])[CH2:18][P+](C1C=CC=CC=1)(C1C=CC=CC=1)C1C=CC=CC=1.C([Li])CCC.[O-:48]S([O-])(=O)=O.[Mg+2].[O-][Mn](=O)(=O)=O.[K+]>S(Cl)(Cl)=O.CN(C)C=O.C1(C)C=CC=CC=1.O>[Br:1][C:2]1[CH:3]=[C:4]([C:5](=[O:7])[C:18]([C:17]2[CH:38]=[CH:39][C:40]([O:41][CH3:42])=[C:15]([CH3:14])[CH:16]=2)=[O:48])[CH:8]=[CH:9][C:10]=1[C:11]#[N:12]

Komponenten

10

Edukt 5

HCID 24083Sulfuric acid magnesium salt (1:1)HCID 516875Potassium PermanganateHCID 461800353-Methyl-4-methoxybenzyl triphenylphosphonium chlorideHCID 534255203-Bromo-4-cyanobenzoic acidHCID 178418339Butyllithium

Produkt 1

HCID 686800872-Bromo-4-[(4-methoxy-3-methylphenyl)(oxo)acetyl]benzonitrileAusbeute 69 %

Reagenzien, Katalysatoren, Lösungsmittel 4

HCID 6228DimethylformamideKatalysatorHCID 962WaterLösungsmittelHCID 1140TolueneLösungsmittel2×HCID 24386Thionyl ChlorideLösungsmittel

Reaktionsbedingungen

Temperatur
0 °C

Versuchsvorschrift

A suspension of 3-bromo-4-cyanobenzoic acid (1.65 g, 7.28 mmol) in thionyl chloride (10 mL) is treated with 3 drops of N,N-dimethylformamide, heated at reflux temperature for 1 h and concentrated in vacuo. This acid chloride residue is re-evaporated 3× with toluene to remove any remaining thionyl chloride. A mixture of 3-methyl-4-methoxybenzyl triphenylphosphonium chloride (6.3 g, 14.55 mmol) in toluene at 0° C. is treated dropwise with n-butyllithium (6.1 mL, 2.5 M in hexanes), allowed to come to room temperature, stirred for 2 h, cooled to 0° C., treated dropwise with a solution of the above-obtained acid chloride in toluene, allowed to come to room temperature, stirred for 2 h, quenched with water and concentrated in vacuo. The resultant residue is dispersed in acetone and water, treated with MgSO4 (7.5 g, 62.5 mmol) and KMnO4 (2.18 g, 13.8 mmol), vigorously stirred at 45° C. for 18 h and filtered. The filtrate is diluted with EtOAc, washed sequentially with water and brine, dried over MgSO4 and evaporated to dryness. This residue is purified by flash chromatography (SiO2, 2/1 hexanes/EtOAc as eluent) to afford the title compound as a yellow solid, 1.8 g (69% yield), identified by HNMR and mass spectral analyses. MS m/e 357 (M+H)+; 1H NMR (400 MHz, DMSO-d6) δ 2.21 (s, 3H), 3.93 (s, 3H), 7.15 (d, J=8.54 Hz, 1H), 7.81 (d, J=1.38 Hz, 1H),7.85 (dd, J=8.54, 2.14 Hz, 1H), 8.03 (dd, J=8.08, 1.52 Hz 1H), 8.18 (d, J=8.08 Hz, 1H), 8.30 (d, J=1.38 Hz, 1H).

Aufarbeitung

  1. temperatureheated
  2. temperatureat reflux temperature for 1 h
  3. concentrationconcentrated in vacuo
  4. customThis acid chloride residue is re-evaporated 3× with toluene
  5. customto remove any remaining thionyl chloride
  6. customto come to room temperature
  7. customto come to room temperature
  8. stirringstirred for 2 h
  9. customquenched with water
  10. concentrationconcentrated in vacuo
  11. additionThe resultant residue is dispersed in acetone
  12. stirringvigorously stirred at 45° C. for 18 h
  13. filtrationfiltered
  14. additionThe filtrate is diluted with EtOAc
  15. washwashed sequentially with water and brine
  16. dry with materialdried over MgSO4
  17. customevaporated to dryness
  18. customThis residue is purified by flash chromatography (SiO2, 2/1 hexanes/EtOAc as eluent)

Quellen und Nachweise

ORD-Eintrag
ord-673a5e9125934bf1a243b33119e1504c
Quelldatensatz
uspto-grants-2009_01
Patentnummer
US07482349B2

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