Water → 2-(3-Fluoro-2-methyl-benzyl)-3-phenyl-indolizine-1-carboxylic acid methyl ester

HRID 1963092Notes

Reaction equation

HRID 1963092 reaction equation
[CH3:1][O:2][C:3]([C:5]1[C:6]([CH2:14][C:15]2[CH:20]=[CH:19][CH:18]=[C:17]([F:21])[C:16]=2[CH3:22])=[CH:7][N:8]2[C:13]=1[CH:12]=[CH:11][CH:10]=[CH:9]2)=[O:4].I[C:24]1[CH:29]=[CH:28][CH:27]=[CH:26][CH:25]=1.C([O-])(=O)C.[K+].O>CN1C(=O)CCC1.C(Cl)Cl.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>[CH3:1][O:2][C:3]([C:5]1[C:6]([CH2:14][C:15]2[CH:20]=[CH:19][CH:18]=[C:17]([F:21])[C:16]=2[CH3:22])=[C:7]([C:24]2[CH:29]=[CH:28][CH:27]=[CH:26][CH:25]=2)[N:8]2[C:13]=1[CH:12]=[CH:11][CH:10]=[CH:9]2)=[O:4]

Participants

8

Reactant 4

HCID 962WaterHCID 11575IodobenzeneHCID 517044Potassium AcetateHCID 677725592-(3-Fluoro-2-methyl-benzyl)indolizine-1-carboxylic acid methyl ester

Product 1

HCID 677721232-(3-Fluoro-2-methyl-benzyl)-3-phenyl-indolizine-1-carboxylic acid methyl esterYield 32.4%

Reagents, catalysts & solvents 3

HCID 178418476HCID 178418476, compoundCatalystHCID 6344DichloromethaneSolventHCID 13387N-methyl-2-pyrrolidoneSolvent

Procedure

The compound of step 2 (1.79 g, 6.02 mmol), iodo-benzene (1.47 g, 7.22 mmol), potassium acetate (1.18 g, 12.03 mmol) and bis(triphenylphosphine)palladium(II) chloride (844 mg, 1.20 mmol) in NMP were heated at 100° C. for 10 min under argon. Then water (844 mg, 36.10 mmol) was added and heating continued for 12 h. The mixture was cooled to room temperature, diluted with DCM and washed with water. The organic phase was dried over sodium sulfate, and evaporated. The residue was purified by silica gel chromatography (HEP/EA) to give 729 mg of the title compound.

Workup

  1. temperatureheating
  2. washwashed with water
  3. dry with materialThe organic phase was dried over sodium sulfate
  4. customevaporated
  5. customThe residue was purified by silica gel chromatography (HEP/EA)

Sources & evidence

ORD record
ord-e1a768efc37e48a799de33a4a4a29ab8
Source dataset
uspto-grants-2013_04
Patent number
US08415336B2

Reaction notes

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