4-Iodo-1-tritylimidazole → Methyl 3-fluoro-2-(1-trityl-1H-imidazol-4-yl)benzoate

HRID 1774934Notes

Reaction equation

HRID 1774934 reaction equation
I[C:2]1[N:3]=[CH:4][N:5]([C:7]([C:20]2[CH:25]=[CH:24][CH:23]=[CH:22][CH:21]=2)([C:14]2[CH:19]=[CH:18][CH:17]=[CH:16][CH:15]=2)[C:8]2[CH:13]=[CH:12][CH:11]=[CH:10][CH:9]=2)[CH:6]=1.CC[Mg+].[Br-].Br[C:31]1[C:40]([F:41])=[CH:39][CH:38]=[CH:37][C:32]=1[C:33]([O:35][CH3:36])=[O:34]>C1COCC1.C(Cl)Cl.[Cl-].[Cl-].[Zn+2].C1C=CC([P]([Pd]([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)[P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)=CC=1>[F:41][C:40]1[C:31]([C:2]2[N:3]=[CH:4][N:5]([C:7]([C:8]3[CH:13]=[CH:12][CH:11]=[CH:10][CH:9]=3)([C:14]3[CH:19]=[CH:18][CH:17]=[CH:16][CH:15]=3)[C:20]3[CH:25]=[CH:24][CH:23]=[CH:22][CH:21]=3)[CH:6]=2)=[C:32]([CH:37]=[CH:38][CH:39]=1)[C:33]([O:35][CH3:36])=[O:34]

Participants

8

Reactant 3

HCID 6182524-Iodo-1-tritylimidazoleHCID 12192162Methyl 2-bromo-3-fluorobenzoateHCID 178461630HCID 178461630, compound

Product 1

HCID 70874744Methyl 3-fluoro-2-(1-trityl-1H-imidazol-4-yl)benzoateYield 41.1%

Reagents, catalysts & solvents 4

HCID 3007855ZincchlorideCatalystHCID 178418397HCID 178418397, compoundCatalystHCID 6344DichloromethaneSolventHCID 8028TetrahydrofuranSolvent2×

Procedure

To a stirred solution of 4-iodo-1-trityl-1H-imidazole (436 mg, 1.0 mmol) in anhydrous THF (6 mL) was added EtMgBr (3.0 M in THF, 1.20 mmol, 0.40 mL) under an atmosphere of N2. The resulting solution was allowed to stir for 90 min and ZnCl2 (0.5 M in THF, 2.40 mL, 1.20 mmol) was added. The resulting white suspension was allowed to stir for 90 min and a solution of methyl 2-bromo-3-fluorobenzoate (280 mg, 1.20 mmol) in THF (1 mL) was added followed by the immediate addition of Pd(PPh3)4 (58 mg, 0.05 mmol). The reaction mixture was allowed to stir at 90° C. for 18 h under an atmosphere of N2. After cooling to room temperature, the solution was diluted with CH2Cl2 (20 mL) and the organic layer was washed with an EDTA (aq) buffer (pH=9) (2×5 mL) and brine. The organic layer was dried (Na2SO4) and concentrated under reduced pressure. The crude residue was purified by flash column chromatography to afford the desired product as yellow oil (190 mg, 41%). 1H NMR: 3.93 (s, 3H), 7.12-7.59 (m, 18H), 7.56 (s, 1H), 7.73-7.75 (m, 1H).

Workup

  1. stirringto stir for 90 min
  2. stirringto stir at 90° C. for 18 h under an atmosphere of N2
  3. washthe organic layer was washed with an EDTA (aq) buffer (pH=9) (2×5 mL) and brine
  4. dry with materialThe organic layer was dried (Na2SO4)
  5. concentrationconcentrated under reduced pressure
  6. customThe crude residue was purified by flash column chromatography

Sources & evidence

ORD record
ord-8870b0039dd54740820e0d3233671c31
Source dataset
uspto-grants-2016_02
Patent number
US09260434B2

Reaction notes

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