2-Dicyclohexylphosphino-2',6'-dimethoxybiphenyl → Methyl 5-cyano-3-methoxypicolinate

HRID 1526568Notes

Reaction equation

HRID 1526568 reaction equation
C1(P(C2CCCCC2)C2C=CC=CC=2C2C(OC)=CC=CC=2OC)CCCCC1.C([Zn][C:33]#[N:34])#N.Cl[C:36]1[CH:37]=[C:38]([O:46][CH3:47])[C:39]([C:42]([O:44][CH3:45])=[O:43])=[N:40][CH:41]=1>CN(C=O)C.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.[Pd].[Pd]>[C:41]([C:36]1[CH:37]=[C:38]([O:46][CH3:47])[C:39]([C:42]([O:44][CH3:45])=[O:43])=[N:34][CH:33]=1)#[N:40]

Participants

6

Reactant 3

HCID 112698722-Dicyclohexylphosphino-2',6'-dimethoxybiphenylHCID 86732279Methyl 5-chloro-3-methoxypicolinateHCID 178514179HCID 178514179, compound

Product 1

HCID 86732280Methyl 5-cyano-3-methoxypicolinateYield 87%

Reagents, catalysts & solvents 2

HCID 9811564Bis(dibenzylideneacetone)palladiumCatalystHCID 6228DimethylformamideSolvent

Conditions

Temperature
120 °C

Procedure

In a 350-mL resealable vessel, Pd2dba3 (1.487 g, 1.623 mmol), dicyclohexyl(2′,6′-dimethoxy-[1,1′-biphenyl]-2-yl)phosphine (1.444 g, 3.52 mmol), dicyanozinc (3.18 g, 27.1 mmol), and methyl 5-chloro-3-methoxypicolinate (step 1, 5.455 g, 27.1 mmol) were taken up in DMF (80 mL). The reaction mixture was purged with Argon and subsequently heated to 120° C. for 2 h. Upon cooling, the reaction mixture was concentrated under reduced pressure. The residue was filtered through Celite, and the filter cake was rinsed with 1% MeOH/DCM. The filtrate was concentrated under reduced pressure and the residue was purified by silica gel chromatography (33%-40% EtOAc/hexane) to afford the title compound as a white solid (4.51 g, 23.5 mmol, 87%). MS m/z=193 [M+H]+. Calculated for C9H8N2O3: 192. 1H NMR in CDCl3 δ: 8.51 (d, 1H, J=1.6), 7.55 (d, 1H, J=1.6), 4.00 (s, 3H), 3.97 (s, 3H).

Workup

  1. customThe reaction mixture was purged with Argon
  2. temperatureUpon cooling
  3. concentrationthe reaction mixture was concentrated under reduced pressure
  4. filtrationThe residue was filtered through Celite
  5. washthe filter cake was rinsed with 1% MeOH/DCM
  6. concentrationThe filtrate was concentrated under reduced pressure
  7. customthe residue was purified by silica gel chromatography (33%-40% EtOAc/hexane)

Sources & evidence

ORD record
ord-5d8b0a1540ff4b508bbf63ec608abbf5
Source dataset
uspto-grants-2015_07
Patent number
US09085576B2

Reaction notes

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