Potassium Carbonate → Methyl 6-(1-methyl-1,2,3,4-tetrahydroquinoxalin-6-yl)-3-(3-phenoxypropoxy)picolinate

HRID 2178245Notes

Reaction equation

HRID 2178245 reaction equation
Br[C:2]1[N:7]=[C:6]([C:8]([O:10][CH3:11])=[O:9])[C:5]([O:12][CH2:13][CH2:14][CH2:15][O:16][C:17]2[CH:22]=[CH:21][CH:20]=[CH:19][CH:18]=2)=[CH:4][CH:3]=1.[CH3:23][N:24]1[C:33]2[C:28](=[CH:29][C:30](B3OC(C)(C)C(C)(C)O3)=[CH:31][CH:32]=2)[NH:27][CH2:26][CH2:25]1.C([O-])([O-])=O.[K+].[K+]>O1CCOCC1.[Br-].C([N+](CCCC)(CCCC)CCCC)CCC.O.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>[CH3:23][N:24]1[C:33]2[C:28](=[CH:29][C:30]([C:2]3[N:7]=[C:6]([C:8]([O:10][CH3:11])=[O:9])[C:5]([O:12][CH2:13][CH2:14][CH2:15][O:16][C:17]4[CH:22]=[CH:21][CH:20]=[CH:19][CH:18]=4)=[CH:4][CH:3]=3)=[CH:31][CH:32]=2)[NH:27][CH2:26][CH2:25]1

Participants

8

Reactant 3

HCID 11430Potassium CarbonateHCID 594187141-Methyl-1,2,3,4-tetrahydroquinoxaline-6-boronic Acid Pinacol EsterHCID 59418768HCID 59418768, compound

Product 1

HCID 59418688Methyl 6-(1-methyl-1,2,3,4-tetrahydroquinoxalin-6-yl)-3-(3-phenoxypropoxy)picolinateYield 16.4%

Reagents, catalysts & solvents 4

HCID 74236Tetrabutylammonium BromideCatalystHCID 178418476HCID 178418476, compoundCatalystHCID 962WaterSolvent2×HCID 312751,4-DioxaneSolvent2×

Conditions

Temperature
100 °C

Procedure

Methyl 6-bromo-3-(3-phenoxypropoxy)picolinate (26C) (141 mg, 0.38 mmol) in 1,4-dioxane (1.0 mL) was added dropwise to a mixture of 1-methyl-6-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1,2,3,4-tetrahydroquinoxaline (25F) (105 mg, 0.38 mmol), K2CO3 (207 mg, 1.52 mmol), tetrabutylammonium bromide (12.1 mg, 0.038 mmol), and dichlorobis(triphenylphosphine)palladium(II) (11.3 mg, 0.015 mmol) in 1,4-dioxane (2.5 mL) and water (1.3 mL) at rt. The mixture was microwave (150 W) heated to 100° C. for 5 min, cooled, diluted with water and extracted with EtOAc. The organic phases were washed with brine, dried over Na2SO4, filtered, and concentrated under reduced pressure. The crude material was purified by flash column chromatography on silica gel eluting with a gradient of PE:EtOAc 100:0-70:30, to provide 27 mg (16%) of the desired product methyl 6-(1-methyl-1,2,3,4-tetrahydroquinoxalin-6-yl)-3-(3-phenoxypropoxy)picolinate (26D): 1H NMR (300 MHz, CDCl3) δ 7.71-7.23 (6H, m), 6.92 (3H, m), 6.58 (1H, d), 4.31-4.13 (6H, m), 3.98 (2H, t), 3.92 (3H, s), 2.30 (2H, t).

Workup

  1. temperaturecooled
  2. extractionextracted with EtOAc
  3. washThe organic phases were washed with brine
  4. dry with materialdried over Na2SO4
  5. filtrationfiltered
  6. concentrationconcentrated under reduced pressure
  7. customThe crude material was purified by flash column chromatography on silica gel eluting with a gradient of PE

Sources & evidence

ORD record
ord-c44130da0e194708bfaf19806f733ebf
Source dataset
uspto-grants-2015_06
Patent number
US09067928B2

Reaction notes

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