Potassium Carbonate → Tert-butyl 5-(pyrazin-2-yl)picolinate

HRID 711289Notes

Reaction equation

HRID 711289 reaction equation
Br[C:2]1[CH:3]=[CH:4][C:5]([C:8]([O:10][C:11]([CH3:14])([CH3:13])[CH3:12])=[O:9])=[N:6][CH:7]=1.CC1(C)C(C)(C)OB(B2OC(C)(C)C(C)(C)O2)O1.CC([O-])=O.[K+].C([O-])([O-])=O.[K+].[K+].Cl[C:45]1[CH:50]=[N:49][CH:48]=[CH:47][N:46]=1>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].C(Cl)Cl.C1COCC1>[C:11]([O:10][C:8](=[O:9])[C:5]1[CH:4]=[CH:3][C:2]([C:45]2[CH:50]=[N:49][CH:48]=[CH:47][N:46]=2)=[CH:7][N:6]=1)([CH3:14])([CH3:13])[CH3:12]

Participants

8

Reactant 5

HCID 11430Potassium CarbonateHCID 73277ChloropyrazineHCID 517044Potassium AcetateHCID 2733548Bis(pinacolato)diboraneHCID 24997839tert-Butyl 5-bromopyridine-2-carboxylate

Product 1

HCID 67208621Tert-butyl 5-(pyrazin-2-yl)picolinate

Reagents, catalysts & solvents 2

HCID 178418807HCID 178418807, compoundCatalyst2×HCID 8028TetrahydrofuranSolvent

Conditions

Temperature
80 °C

Procedure

The 250 mL flask was charged with tert-butyl 5-bromopicolinate 34h-4 (12.9 g, 50 mmol), 4,4,4′,4′,5,5,5′,5′-octamethyl-2,2′-bi(1,3,2-dioxaborolane) (13.9 g, 55 mmol), KOAc (9.8 g, 100 mmol), PdCl2(dppf)-CH2Cl2 adduct (0.408 g, 0.5 mmol) and THF (80 mL). The flask was sealed under nitrogen and the mixture was stirred at 80° C. for 24 hours. After completion of the reaction, it was cooled to room temperature and filtered through Celite. The filtrate was taken in 500 mL 4-necked RB flask and charged with aqueous K2CO3 solution (13.8 g in 100 ml Of water), 2-chloropyrazine (6.8 g, 60 mmol), and PdCl2(dppf)-CH2Cl2 adduct (0.204 g, 0.25 mmol). The reaction mixture was stirred at 64° C. for 2 h under nitrogen, cooled to room temperature and filtered through Celite. The filtrate was diluted with i-PrOAc (100 mL) and the aqueous layer separated. The organic layer was washed with water (2×100 mL), concentrated to ˜20 mL of volume and diluted with heptane (200 mL). The solid was collected by filtration, washed with heptane (50 mL), and dried at 40° C. to obtain 34h-1 as a pale yellow solid.

Workup

  1. customThe flask was sealed under nitrogen
  2. customAfter completion of the reaction, it
  3. temperaturewas cooled to room temperature
  4. filtrationfiltered through Celite
  5. stirringThe reaction mixture was stirred at 64° C. for 2 h under nitrogen
  6. temperaturecooled to room temperature
  7. filtrationfiltered through Celite
  8. additionThe filtrate was diluted with i-PrOAc (100 mL)
  9. customthe aqueous layer separated
  10. washThe organic layer was washed with water (2×100 mL)
  11. concentrationconcentrated to ˜20 mL of volume
  12. additiondiluted with heptane (200 mL)
  13. filtrationThe solid was collected by filtration
  14. washwashed with heptane (50 mL)
  15. customdried at 40° C.
  16. customto obtain 34h-1 as a pale yellow solid

Sources & evidence

ORD record
ord-2e7a69acf6624149bd822dccc176c791
Source dataset
uspto-grants-2015_11
Patent number
US09181235B2

Reaction notes

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