1-(Bromomethyl)-2-fluoro-4-iodobenzene → HCID 68483814, compound

HRID 2381148Notes

Reaction equation

HRID 2381148 reaction equation
[NH:1]1[C:5]2=[CH:6][N:7]=[CH:8][CH:9]=[C:4]2[CH:3]=[C:2]1[C:10]([O:12][CH3:13])=[O:11].[CH3:14]C(C)([O-])C.[K+].[F:20][C:21]1[CH:28]=[C:27]([I:29])[CH:26]=[CH:25][C:22]=1[CH2:23]Br>CN(C=O)C>[F:20][C:21]1[CH:28]=[C:27]([I:29])[CH:26]=[CH:25][C:22]=1[CH2:23][N:1]1[C:5]2=[CH:6][N:7]=[CH:8][CH:9]=[C:4]2[CH:3]=[C:2]1[C:10]([O:12][CH2:13][CH3:14])=[O:11]

Participants

5

Reactant 3

HCID 222404061-(Bromomethyl)-2-fluoro-4-iodobenzeneHCID 23665647Potassium tert-butoxideHCID 45480461Methyl 1H-pyrrolo[2,3-c]pyridine-2-carboxylate

Product 1

HCID 68483814HCID 68483814, compoundYield 46%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent2×

Conditions

Temperature
60 °C

Procedure

To a suspension of methyl 1H-pyrrolo[2,3-c]pyridine-2-carboxylate (0.81 g, 4.26 mmol) in DMF (15 ml) was added potassium tert-butoxide (0.72 g, 6.39 mmol). After the resultant red-brown suspension had been stirred for 40 minutes, a solution of 2-fluoro-4-iodobenzyl bromide (2.01 g, 6.39 mmol) in DMF (5 ml) was added dropwise over 10 minutes. The suspension was then heated to 60° C. for 35 minutes before stirring at room temperature for 18 hours. The reaction mixture was concentrated in vacuo, the resultant residue partitioned between dichloromethane (40 ml) and water (30 ml) and the organic layer separated. The aqueous layer was extracted with dichloromethane (2×25 ml) and the combined organic extracts were washed with brine (30 ml) dried over magnesium sulphate, then concentrated in vacuo to provide a residue. The residue was purified by flash chromatography (Si-SPE, dichloromethane:ethyl acetate 100:0 to 50:50 to 0:100 then dichloromethane:methanol 90:10 to 80:20) gave the title compound as a pale cream solid (0.83 g, 46%). LCMS (method B): RT=2.58 min, M+H+=425.

Workup

  1. stirringbefore stirring at room temperature for 18 hours
  2. concentrationThe reaction mixture was concentrated in vacuo
  3. customthe resultant residue partitioned between dichloromethane (40 ml) and water (30 ml)
  4. customthe organic layer separated
  5. extractionThe aqueous layer was extracted with dichloromethane (2×25 ml)
  6. washthe combined organic extracts were washed with brine (30 ml)
  7. dry with materialdried over magnesium sulphate
  8. concentrationconcentrated in vacuo
  9. customto provide a residue
  10. customThe residue was purified by flash chromatography (Si-SPE, dichloromethane:ethyl acetate 100:0 to 50:50 to 0:100

Sources & evidence

ORD record
ord-9f8f223b8e174ece9d01d83672b43eff
Source dataset
uspto-grants-2012_09
Patent number
US08258152B2

Reaction notes

Loading…