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

HRID 498232

Reaction equation

HRID 498232 reaction equation
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:18]([C:21]1C=C(B(O)O)C=CC=1)([OH:20])=[O:19].BrC1C(C)=N[CH:34]=[CH:35][CH:36]=1.O=S(Cl)Cl.[C:42](#N)C>C([O-])([O-])=O.[Na+].[Na+]>[C:35]([O:20][C:18](=[O:19])[CH2:21][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])([CH3:34])([CH3:36])[CH3:42]

Participants

7

Reactant 5

HCID 6342AcetonitrileHCID 24386Thionyl ChlorideHCID 12010033-Bromo-2-methylpyridineHCID 27339573-Carboxyphenylboronic acidHCID 69489264Methyl 3-(6-methylpyridin-3-yl)benzoate

Product 1

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

Reagents, catalysts & solvents 1

HCID 10340Sodium CarbonateSolvent

Procedure

The title compound 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 2000, 829). 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). Obtained as a yellow oil (4.73 g).

Workup

  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. Synlett 2000, 829)
  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

Sources & evidence

ORD record
ord-706be29a808a474ab8870fa03ff14c51
Source dataset
uspto-grants-2005_09
Patent number
US06949542B2

Linked notes

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