Water → Methyl 6'-chloro-2,2'-bipyridine-3-carboxylate

HRID 1479894Notes

Reaction equation

HRID 1479894 reaction equation
Br[C:2]1[N:11]=[CH:10][CH:9]=[CH:8][C:3]=1[C:4]([O:6][CH3:7])=[O:5].[Cl:12][C:13]1[CH:18]=[CH:17][CH:16]=[C:15](B2OC(C)(C)C(C)(C)O2)[N:14]=1.C([O-])([O-])=O.[K+].[K+].O>O1CCOCC1.Cl[Pd](Cl)([P](C1C=CC=CC=1)(C1C=CC=CC=1)C1C=CC=CC=1)[P](C1C=CC=CC=1)(C1C=CC=CC=1)C1C=CC=CC=1>[Cl:12][C:13]1[N:14]=[C:15]([C:2]2[C:3]([C:4]([O:6][CH3:7])=[O:5])=[CH:8][CH:9]=[CH:10][N:11]=2)[CH:16]=[CH:17][CH:18]=1

Participants

7

Reactant 4

HCID 962Water2×HCID 11430Potassium CarbonateHCID 12349191Methyl 2-bromopyridine-3-carboxylateHCID 177504912-Chloro-6-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)pyridine

Product 1

HCID 90040631Methyl 6'-chloro-2,2'-bipyridine-3-carboxylate

Reagents, catalysts & solvents 2

HCID 178418476HCID 178418476, compoundCatalystHCID 312751,4-DioxaneSolvent

Procedure

0.49 g (0.70 mmol) of (Ph3P)2PdCl2 is added under argan to a solution of 3.0 g (13.9 mmol) of methyl 2-bromonicotinate in 10 ml of dioxane and the mixture is stirred for 30 min at room temperature. Thereafter, 3.33 g (13.78 mmol) of 2-chloro-6-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)pyridine, 5.76 g (41.68 mmol) of K2CO3 and 11 ml of H2O are added in succession to the mixture, and the mixture is stirred for 6 hours under reflux and subsequently allowed to stand overnight at room temperature (RT). For work-up, the reaction mixture is poured into 150 ml of H2O and extracted repeatedly with CH2Cl2. The combined organic phases are dried over Na2SO4 and subsequently concentrated. The crude product thus obtained is purified by chromatography on silica gel using heptane/ethyl acetate (7:3) as the mobile phase. This gives 2.50 g (72%) of product as a colorless oil; 1H NMR (CDCl3) δ 8.70 (dd, 1H), 8.15 (dd, 1H), 7.95 (dd, 1H), 7.80 (dd, 1H), 7.40 (dd, 1H), 7.37 (dd, 1H), 3.90 (s, 3H, COOMe).

Workup

  1. stirringthe mixture is stirred for 6 hours
  2. temperatureunder reflux
  3. waitto stand overnight at room temperature
  4. custom(RT)
  5. extractionextracted repeatedly with CH2Cl2
  6. dry with materialThe combined organic phases are dried over Na2SO4
  7. concentrationsubsequently concentrated

Sources & evidence

ORD record
ord-307fde82bb4e48f7a7b68f437d3bd049
Source dataset
uspto-grants-2016_08
Patent number
US09409881B2

Reaction notes

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