Thionyl Chloride → 3-[3-(2-Methyl-pyridin-3-yl)-phenyl]-3-oxo-propionic acid tert-butyl ester

HRID 498233Notes

Reaction equation

HRID 498233 reaction equation
CO[C:3](=[O:17])[C:4]1[CH:9]=[CH:8][CH:7]=[C:6]([C:10]2[C:11]([CH3:16])=[N:12][CH:13]=[CH:14][CH:15]=2)[CH:5]=1.[C:18]([C:21]1[CH:22]=C(B(O)O)C=C[CH:26]=1)(O)=O.BrC1C(C)=NC=CC=1.[O-]P([O-])([O-])=O.[K+].[K+].[K+].[O:46]=S(Cl)Cl.[O:50]1[CH2:55][CH2:54]OCC1>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:21]([O:46][C:55](=[O:50])[CH2:54][C:3]([C:4]1[CH:9]=[CH:8][CH:7]=[C:6]([C:10]2[C:11]([CH3:16])=[N:12][CH:13]=[CH:14][CH:15]=2)[CH:5]=1)=[O:17])([CH3:18])([CH3:26])[CH3:22]

Participants

8

Reactant 6

HCID 24386Thionyl ChlorideHCID 312751,4-DioxaneHCID 62657Potassium Phosphate, TribasicHCID 12010033-Bromo-2-methylpyridineHCID 27339573-Carboxyphenylboronic acidHCID 694871813-(2-Methyl-pyridin-3-yl)-benzoic acid methyl ester

Product 1

HCID 694892323-[3-(2-Methyl-pyridin-3-yl)-phenyl]-3-oxo-propionic acid tert-butyl ester

Reagents, catalysts & solvents 1

HCID 178418397HCID 178418397, compoundCatalyst

Procedure

The title compound was prepared from 3-(2-methyl-pyridin-3-yl)-benzoic acid methyl ester [prepared by the following procedure: A mixture of 3-carboxyphenylboronic acid (3.96 g, 23.85 mmol), 3-bromo-2-methylpyridine (5.23 g, 21.68 mmol) and K3PO4 (7.60 g, 35.78 mmol) in dioxane (112 mL) was degassed and Pd(Ph3P)4 (1.37 g, 1.2 mmol) was added. The reaction mixture was refluxed for 5 h, evaporated to dryness. The residue was suspended in MeOH (320 mL) and SOCl2 (7.87 mL, 108.4 mmol) was added dropwise at 23° C. and the reaction mixture was refluxed for 16 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 solid, which was purified by silica gel column chromatography with cyclohexane/EtOAc.] (2.65 g, 11.66 mmol) by treatment with lithium tert-butyl acetate according to general procedure K (method b). Obtained as a colorless oil (2.62 g).

Workup

  1. customprepared by the following procedure
  2. customwas degassed
  3. temperatureThe reaction mixture was refluxed for 5 h
  4. customevaporated to dryness
  5. temperaturethe reaction mixture was refluxed for 16 h
  6. customEvaporated to dryness
  7. washwashed with sat. NaHCO3-solution and brine
  8. dry with materialdried over Na2SO4
  9. customRemoval of the solvent in vacuum
  10. waitleft a brown solid, which
  11. customwas purified by silica gel column chromatography with cyclohexane/EtOAc

Sources & evidence

ORD record
ord-654db7ab333d4d4d9dec827cb94f33e2
Source dataset
uspto-grants-2005_09
Patent number
US06949542B2

Reaction notes

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