Potassium Fluoride → Methyl 1-[2-(4-tert-butoxyphenoxy)ethyl]-4-(3-ethoxyphenyl)-1H-pyrrolo[3,2-c]pyridine-2-carboxylate

HRID 513198Notes

Reaction equation

HRID 513198 reaction equation
[C:1]([O:5][C:6]1[CH:28]=[CH:27][C:9]([O:10][CH2:11][CH2:12][N:13]2[C:21]3[CH:20]=[CH:19][N:18]=[C:17](Cl)[C:16]=3[CH:15]=[C:14]2[C:23]([O:25][CH3:26])=[O:24])=[CH:8][CH:7]=1)([CH3:4])([CH3:3])[CH3:2].[CH2:29]([O:31][C:32]1[CH:33]=[C:34](B(O)O)[CH:35]=[CH:36][CH:37]=1)[CH3:30].[F-].[K+]>O1CCOCC1.CC(C)([P](C(C)(C)C)([Pd][P](C(C)(C)C)(C(C)(C)C)C(C)(C)C)C(C)(C)C)C>[C:1]([O:5][C:6]1[CH:28]=[CH:27][C:9]([O:10][CH2:11][CH2:12][N:13]2[C:21]3[CH:20]=[CH:19][N:18]=[C:17]([C:36]4[CH:35]=[CH:34][CH:33]=[C:32]([O:31][CH2:29][CH3:30])[CH:37]=4)[C:16]=3[CH:15]=[C:14]2[C:23]([O:25][CH3:26])=[O:24])=[CH:8][CH:7]=1)([CH3:4])([CH3:3])[CH3:2]

Participants

6

Reactant 3

HCID 522689Potassium FluorideHCID 27739203-Ethoxybenzeneboronic acidHCID 86720574Methyl 1-[2-(4-tert-butoxyphenoxy)ethyl]-4-chloro-1H-pyrrolo[3,2-c]pyridine-2-carboxylate

Product 1

HCID 71230449Methyl 1-[2-(4-tert-butoxyphenoxy)ethyl]-4-(3-ethoxyphenyl)-1H-pyrrolo[3,2-c]pyridine-2-carboxylateYield 77.4%

Reagents, catalysts & solvents 2

HCID 178418851HCID 178418851, compoundCatalystHCID 312751,4-DioxaneSolvent

Procedure

Methyl 1-[2-(4-tert-butoxyphenoxy)ethyl]-4-chloro-1H-pyrrolo[3,2-c]pyridine-2-carboxylate (1 g, 2.482 mmole), 3-ethoxyphenylboronic acid (0.618 g, 3.72 mmole), KF (0.433 g, 7.45 mmole), and bis(tri-t-butylphosphine)palladium(0) (0.127 g, 0.248 mmole) were combined in 1,4-dioxane (10 mL). The mixture was degassed (3× pump/N2) then heated to reflux. After 5 hr the mixture was cooled to RT, diluted with EtOAc, filtered through a pad of Celite washing with EtOAc, and concentrated. Flash column chromatography (Biotage-SNAP-50 g SiO2, 0-30% EtOAc/hexanes) gave the title compound (939 mg, 77%) as an off-white foam. 1H NMR (400 MHz, CDCl3): 8.52 (d, J=6.0 Hz, 1 H); 7.61 (d, J=0.9 Hz, 1 H); 7.52-7.47 (m, 2 H); 7.43 (d, J=7.2 Hz, 2

Workup

  1. customThe mixture was degassed (3× pump/N2)
  2. temperaturethen heated to reflux
  3. additiondiluted with EtOAc
  4. filtrationfiltered through a pad of Celite
  5. washwashing with EtOAc
  6. concentrationconcentrated

Sources & evidence

ORD record
ord-72279688011a4906bc6fef5e1ef4e440
Source dataset
uspto-grants-2015_08
Patent number
US09102673B2

Reaction notes

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