Thionyl Chloride → 3-[3-(6-Methyl-pyridin-3-yl)-phenyl]-3-oxo-propionic acid tert-butyl ester

HRID 1767593

Reaktionsgleichung

Reaktionsgleichung von HRID 1767593
CO[C:3](=[O:17])[C:4]1[CH:9]=[CH:8][CH:7]=[C:6]([C:10]2[CH:11]=[N:12][C:13]([CH3:16])=[CH:14][CH:15]=2)[CH:5]=1.C(C1C=C(B(O)O)C=CC=1)(O)=O.BrC1C(C)=NC=CC=1.O=S(Cl)Cl.[C:42]([O:46][C:47](=[O:64])[CH2:48]C(C1C=CC=C(C2C=CN=C(C)C=2)C=1)=O)([CH3:45])([CH3:44])[CH3:43]>C(#N)C.C([O-])([O-])=O.[Na+].[Na+]>[C:42]([O:46][C:47](=[O:64])[CH2:48][C:3]([C:4]1[CH:9]=[CH:8][CH:7]=[C:6]([C:10]2[CH:11]=[N:12][C:13]([CH3:16])=[CH:14][CH:15]=2)[CH:5]=1)=[O:17])([CH3:45])([CH3:44])[CH3:43]

Komponenten

8

Edukt 5

HCID 24386Thionyl ChlorideHCID 12010033-Bromo-2-methylpyridineHCID 27339573-Carboxyphenylboronic acidHCID 69489264Methyl 3-(6-methylpyridin-3-yl)benzoateHCID 694893073-[3-(2-Methyl-pyridin-4-yl)-phenyl]-3-oxo-propionic acid tert-butyl ester

Produkt 1

HCID 694893863-[3-(6-Methyl-pyridin-3-yl)-phenyl]-3-oxo-propionic acid tert-butyl ester

Reagenzien, Katalysatoren, Lösungsmittel 2

HCID 6342AcetonitrileLösungsmittelHCID 10340Sodium CarbonateLösungsmittel

Versuchsvorschrift

Compound K3 was prepared from 3-(6-methyl-pyridin-3-yl)-benzoic acid methyl ester [prepared by the following procedure: A mixture of 3-carboxyphenylboronic acid (4.82 g, 29.07 mmol) and 3-bromo-2-methylpyridine (5.00 g, 29.07 mmol) in acetonitrile (145 mL) and 0.4M Na2CO3-solution (145 mL) was degassed and Pd(Ph3P)4 (1.68 g, 5 mol %) was added. The reaction mixture was refluxed for 16 h, evaporated to dryness (cf. Synlett 6:829–831 (2000). The residue was suspended in MeOH (400 mL) and SOCl2 (10.5 mL, 145 mmol) was added dropwise at 23° C. and the reaction mixture was refluxed for 4 h. Evaporated to dryness, taken up in EtOAc, washed with sat. NaHCO3-solution and brine, dried over Na2SO4. Removal of the solvent in vacuum left a brown oil, which was purified by silica gel column chromatography with cyclohexane/EtOAc.] (3.87 g, 17.0 mmol) by treatment with lithium tert-butyl acetate according to general procedure K (method b). Starting from 3-(2-methyl-pyridin-4-yl)-benzoic acid methyl ester, prepared in analogy to the method described above, 3-[3-(2-Methyl-pyridin-4-yl)-phenyl]-3-oxo-propionic acid tert-butyl ester (Compound K4) was prepared in analogy to the above method.

Aufarbeitung

  1. customprepared by the following procedure
  2. customwas degassed
  3. additionPd(Ph3P)4 (1.68 g, 5 mol %) was added
  4. temperatureThe reaction mixture was refluxed for 16 h
  5. customevaporated to dryness (cf
  6. temperaturethe reaction mixture was refluxed for 4 h
  7. customEvaporated to dryness
  8. washwashed with sat. NaHCO3-solution and brine
  9. dry with materialdried over Na2SO4
  10. customRemoval of the solvent in vacuum
  11. waitleft a brown oil, which
  12. customwas purified by silica gel column chromatography with cyclohexane/EtOAc
  13. customprepared in analogy to the method
  14. customwas prepared in analogy to the above method

Quellen und Nachweise

ORD-Eintrag
ord-7697e8f4ce8e4d34b47dbc1d29019b4e
Quelldatensatz
uspto-grants-2007_06
Patentnummer
US07235547B2

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