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

HRID 498238Notes

Reaction equation

HRID 498238 reaction equation
CO[C:3](=[O:18])[C:4]1[CH:9]=[CH:8][CH:7]=[C:6]([C:10]2[CH:11]=[N:12][C:13]([C:16]#[N:17])=[CH:14][CH:15]=2)[CH:5]=1.[C:19]([C:22]1C=C(B(O)O)C=CC=1)([OH:21])=[O:20].BrC1C=[CH:34][C:35]([C:38]#N)=NC=1.O=S(Cl)Cl.[C:44](#N)C>C([O-])([O-])=O.[Na+].[Na+].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:35]([O:21][C:19](=[O:20])[CH2:22][C:3]([C:4]1[CH:9]=[CH:8][CH:7]=[C:6]([C:10]2[CH:11]=[N:12][C:13]([C:16]#[N:17])=[CH:14][CH:15]=2)[CH:5]=1)=[O:18])([CH3:34])([CH3:38])[CH3:44]

Participants

8

Reactant 5

HCID 6342AcetonitrileHCID 24386Thionyl ChlorideHCID 8171545-Bromopyridine-2-carbonitrileHCID 27339573-Carboxyphenylboronic acidHCID 69487036HCID 69487036, compound

Product 1

HCID 694865793-[3-(6-Cyano-pyridin-3-yl)-phenyl]-3-oxo-propionic acid tert-butyl ester

Reagents, catalysts & solvents 2

HCID 178418397HCID 178418397, compoundCatalystHCID 10340Sodium CarbonateSolvent

Conditions

Temperature
23 °C

Procedure

The title compound was prepared from 3-(6-cyano-pyridin-3-yl)-benzoic acid methyl ester [prepared by the following procedure: A mixture of 3-carboxyphenylboronic acid (2.08 g, 12.51 mmol) and 5-bromo-pyridine-2-carbonitrile [CAS-No. 97483-77-7] (2.08 g, 11.37 mmol) in acetonitrile (55 ml) and 0.4M Na2CO3-solution (55 ml) was degassed and Pd(Ph3P)4 (657 mg, 0.57 mmol) was added. The reaction mixture was refluxed for 18 h and evaporated to dryness [Synlett 2000 (6), 829-831]. The residue was suspended in MeOH (300 ml), SOCl2 (2.61 ml, 36 mmol) was added dropwise at 23° C. and the reaction mixture was stirred at 23° C. for 3 days. Concentrated in vacuum to about 100 mL, diluted with EtOAc, washed with sat. NaHCO3-solution and brine, dried over Na2SO4. Removal of the solvent in vacuum left a brown residue, which was purified by silica gel column chromatography with cyclohexane/EtOAc.] (1.38 g, 5.79 mmol) by treatment with lithium tert-butyl acetate according to general procedure K (method b). Obtained as an orange oil (530 mg).

Workup

  1. customprepared by the following procedure
  2. customwas degassed
  3. temperatureThe reaction mixture was refluxed for 18 h
  4. customevaporated to dryness [Synlett 2000 (6), 829-831]
  5. concentrationConcentrated in vacuum to about 100 mL
  6. additiondiluted with EtOAc
  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 residue, which
  11. customwas purified by silica gel column chromatography with cyclohexane/EtOAc

Sources & evidence

ORD record
ord-b45f37b80ca74d30ba73134f894f6cf5
Source dataset
uspto-grants-2005_09
Patent number
US06949542B2

Reaction notes

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