Water → Methyl 3-(2-phenoxyethoxy)-6-(1,2,3,4-tetrahydroquinolin-7-yl)picolinate

HRID 1896598Notes

Reaction equation

HRID 1896598 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][O:15][C:16]2[CH:21]=[CH:20][CH:19]=[CH:18][CH:17]=2)=[CH:4][CH:3]=1.CC1(C)C(C)(C)OB([C:30]2[CH:39]=[C:38]3[C:33]([CH2:34][CH2:35][CH2:36][NH:37]3)=[CH:32][CH:31]=2)O1.C([O-])([O-])=O.[K+].[K+].O>[Br-].C([N+](CCCC)(CCCC)CCCC)CCC.O1CCOCC1.CCOC(C)=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>[O:15]([CH2:14][CH2:13][O:12][C:5]1[C:6]([C:8]([O:10][CH3:11])=[O:9])=[N:7][C:2]([C:30]2[CH:39]=[C:38]3[C:33]([CH2:34][CH2:35][CH2:36][NH:37]3)=[CH:32][CH:31]=2)=[CH:3][CH:4]=1)[C:16]1[CH:21]=[CH:20][CH:19]=[CH:18][CH:17]=1

Participants

9

Reactant 4

HCID 962WaterHCID 11430Potassium CarbonateHCID 594187157-(4,4,5,5-Tetramethyl-1,3,2-dioxaborolan-2-yl)-1,2,3,4-tetrahydroquinolineHCID 59418733Methyl 6-bromo-3-(2-phenoxyethoxy)picolinate

Product 1

HCID 59418754Methyl 3-(2-phenoxyethoxy)-6-(1,2,3,4-tetrahydroquinolin-7-yl)picolinateYield 72.4%

Reagents, catalysts & solvents 4

HCID 74236Tetrabutylammonium BromideCatalystHCID 178418476HCID 178418476, compoundCatalystHCID 8857Ethyl AcetateSolventHCID 312751,4-DioxaneSolvent

Procedure

Methyl 6-bromo-3-(2-phenoxyethoxy)picolinate (27A) (327 mg, 0.93 mmol), 7-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1,2,3,4-tetrahydroquinoline (27B) (181 mg, 0.7 mmol), tetrabutylammonium bromide (30 mg, 0.09 mmol), dichlorobis(triphenylphosphine)palladium(II) (26 mg, 0.04 mmol) and K2CO3 (322 mg, 2.33 mmol) were stirred in 1,4-dioxane (2 mL) and water (1 mL) at 90° C. for 45 minutes. The reaction mixture was allowed to cool to rt and diluted with EtOAc (5 ml), washed with H2O, dried over MgSO4, filtered, and concentrated under reduced pressure. The crude material was purified by column chromatography on silica gel eluting with a gradient of PE/EtOAc 9:1-7:3, to provide 205 mg (72%) of the desired product methyl 3-(2-phenoxyethoxy)-6-(1,2,3,4-tetrahydroquinolin-7-yl)picolinate (27C): 1H NMR (300 MHz, CDCl3) δ7.69 (1H, m), 7.44 (1H, m), 7.27 (2H, m), 7.13 (2H, s), 6.94 (4H, m), 4.40 (2H, m), 4.34 (2H, m), 3.90 (3H, s), 3.27 (2H, t), 2.76 (2H, t), 1.92 (2H, m).

Workup

  1. washwashed with H2O
  2. dry with materialdried over MgSO4
  3. filtrationfiltered
  4. concentrationconcentrated under reduced pressure
  5. customThe crude material was purified by column chromatography on silica gel eluting with a gradient of PE/EtOAc 9:1-7:3

Sources & evidence

ORD record
ord-91b37f2f808848949ce01b4d49657717
Source dataset
uspto-grants-2013_08
Patent number
US08518970B2

Reaction notes

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