Dichloromethane → 2'-Methyl-2-oxo-1,2-dihydro-3,4'-bipyridine-6-carboxylic acid, hydrochloride salt

HRID 2364969Notes

Reaction equation

HRID 2364969 reaction equation
C[O:2][C:3]1[N:8]=[C:7]([C:9]([O:11]C)=[O:10])[CH:6]=[CH:5][C:4]=1B1OC(C)(C)C(C)(C)O1.[Cl:22]CCl.Br[C:26]1[CH:27]=[CH:28][C:29]([C:34](OC)=O)=[N:30][C:31]=1OC.CC1(C)C(C)(C)OB(B2OC(C)(C)C(C)(C)O2)O1.C([O-])(=O)C.[K+]>O1CCOCC1.C1C=CC(P(C2C=CC=CC=2)[C-]2C=CC=C2)=CC=1.C1C=CC(P(C2C=CC=CC=2)[C-]2C=CC=C2)=CC=1.Cl[Pd]Cl.[Fe+2]>[ClH:22].[CH3:34][C:29]1[CH:28]=[C:27]([C:4]2[C:3](=[O:2])[NH:8][C:7]([C:9]([OH:11])=[O:10])=[CH:6][CH:5]=2)[CH:26]=[CH:31][N:30]=1

Participants

8

Reactant 5

HCID 6344DichloromethaneHCID 517044Potassium AcetateHCID 2733548Bis(pinacolato)diboraneHCID 46311222Methyl 5-bromo-6-methoxypicolinateHCID 68380502Methyl 6-methoxy-5-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)picolinate

Product 1

HCID 1317313152'-Methyl-2-oxo-1,2-dihydro-3,4'-bipyridine-6-carboxylic acid, hydrochloride salt

Reagents, catalysts & solvents 2

HCID 178418228Bis(cyclopenta-1,4-dien-1-yl(diphenyl)phosphane);dichloropalladium;iron(2+)CatalystHCID 312751,4-DioxaneSolvent

Conditions

Temperature
100 °C

Procedure

Synthesis of methyl 6-methoxy-5-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)pyridine-2-carboxylate (C31). [1,1′-Bis(diphenylphosphino)ferrocene]dichloropalladium(II), complex with dichloromethane (740 mg, 0.91 mmol) was added in one portion to a degassed mixture of methyl 5-bromo-6-methoxypyridine-2-carboxylate (C30) (7.42 g, 30.2 mmol), 4,4,4′,4′,5,5,5′,5′-octamethyl-2,2′-bi-1,3,2-dioxaborolane (9.19 g, 36.2 mmol) and potassium acetate (8.88 g, 90.5 mmol) in dioxane (150 mL) at room temperature under argon and the reaction was heated at 100° C. for 18 hours. The mixture was cooled to room temperature, filtered through Celite, washed with ethyl acetate (400 mL) and concentrated in vacuo. Silica gel chromatography (Gradient: 15% to 35% ethyl acetate in heptane) afforded the title compound as a colorless oil, which solidified on standing to form a white crystalline solid. Yield: 7.14 g, 24.4 mmol, 81%. LCMS m/z 212.1 (M for boronic acid+1). 1H NMR (400 MHz, CDCl3) δ 1.37 (s, 12H), 3.97 (s, 3H), 4.06 (s, 3H), 7.67 (d, J=7.3 Hz, 1H), 8.09 (d, J=7.3 Hz, 1H). A second crop of material (1.13 g, 13%) was also obtained from the purification; this contained minor impurities by NMR analysis.

Workup

  1. temperatureThe mixture was cooled to room temperature
  2. filtrationfiltered through Celite
  3. washwashed with ethyl acetate (400 mL)
  4. concentrationconcentrated in vacuo

Sources & evidence

ORD record
ord-60fd297cb5ad4734abf11a0ad98a8feb
Source dataset
uspto-grants-2014_04
Patent number
US08697673B2

Reaction notes

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