Lithium Chloride → Methyl 4-(2-ethoxyvinyl)-1-(4-fluorobenzyl)-1H-pyrrolo[2,3-c]pyridine-5-carboxylate

HRID 640698Notes

Reaction equation

HRID 640698 reaction equation
[F:1][C:2]1[CH:29]=[CH:28][C:5]([CH2:6][N:7]2[C:11]3=[CH:12][N:13]=[C:14]([C:24]([O:26][CH3:27])=[O:25])[C:15](OS(C(F)(F)F)(=O)=O)=[C:10]3[CH:9]=[CH:8]2)=[CH:4][CH:3]=1.[Cl-].[Li+].[CH2:32]([O:34][CH:35]=[CH:36][Sn](CCCC)(CCCC)CCCC)[CH3:33]>CN(C=O)C.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>[CH2:35]([O:34][CH:32]=[CH:33][C:15]1[C:14]([C:24]([O:26][CH3:27])=[O:25])=[N:13][CH:12]=[C:11]2[N:7]([CH2:6][C:5]3[CH:28]=[CH:29][C:2]([F:1])=[CH:3][CH:4]=3)[CH:8]=[CH:9][C:10]=12)[CH3:36]

Participants

6

Reactant 3

HCID 433294Lithium ChlorideHCID 2763294(Z)-1-Ethoxy-2-(tributylstannyl)etheneHCID 532374681h-Pyrrolo[2,3-c]pyridine-5-carboxylic acid,1-[(4-fluorophenyl)methyl]-4-[[(trifluoromethyl)sulfonyl]oxy]-,methyl ester

Product 1

HCID 68665270Methyl 4-(2-ethoxyvinyl)-1-(4-fluorobenzyl)-1H-pyrrolo[2,3-c]pyridine-5-carboxylateYield 89.2%

Reagents, catalysts & solvents 2

HCID 178418476HCID 178418476, compoundCatalystHCID 6228DimethylformamideSolvent2×

Conditions

Temperature
79 °C

Procedure

To a solution of methyl 1-(4-fluorobenzyl)-4-{[(trifluoromethyl)sulfonyl]oxy}-1H-pyrrolo[2,3-c]pyridine-5-carboxylate (2 g, 4.62 mmol) in DMF (27 mL) was added lithium chloride (0.59 mg, 13.88 mmol). Dry nitrogen was bubbled through the mixture for for 10 min, and then dichlorobis(triphenylphosphine)palladium(II) (0.16 g, 0.23 mmol) was added. The mixture was heated to 79° C., and a solution of ethoxyvinyl tributyltin (mixture of isomers: 1,2-E:1,2-Z:1,1=1:0: 0.97:0.18) [prepared according to A. Leusik, H. A. Budding, J. W. Marsman, J. Organomet. Chem., 1967, 9, 285-294] (1.82 g, 5.08 mmol) in DMF (23 mL). The resulting mixture was stirred for 9 h at 70° C. under nitrogen atmosphere. It was quenched with saturated sodium chloride and filtered to remove solid precipitate then concentrated. Purification by flash chromatography (Biotage) over silica gel (1:1 to 1:3, hexane/ethyl acetate) afforded the title product as brown glue (1.46 g, 89.2% yield). LCMS (APCl, M+H+): 355.2.

Workup

  1. customDry nitrogen was bubbled through the mixture for for 10 min
  2. customIt was quenched with saturated sodium chloride
  3. filtrationfiltered
  4. customto remove solid precipitate
  5. concentrationthen concentrated
  6. customPurification by flash chromatography (Biotage) over silica gel (1:1 to 1:3, hexane/ethyl acetate)

Sources & evidence

ORD record
ord-3f6e3e12e082489a96a0d48f20c487f0
Source dataset
uspto-grants-2010_04
Patent number
US07692014B2

Reaction notes

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