Methyl iodide → Ethyl 8-fluoro-9-iodo-3-methyl-3,4,5,6-tetrahydro-4,6methanobenzo[3,4]cyclohepta[1,2-d]imidazole-2-carboxylate

HRID 575436Notes

Reaction equation

HRID 575436 reaction equation
[F:1][C:2]1[C:21]([I:22])=[CH:20][C:5]2[C:6]3[N:10]=[C:9]([C:11]([O:13][CH2:14][CH3:15])=[O:12])[NH:8][C:7]=3[CH:16]3[CH2:19][CH:18]([C:4]=2[CH:3]=1)[CH2:17]3.[C:23](=O)([O-])[O-].[K+].[K+].CI>CN(C)C=O>[F:1][C:2]1[C:21]([I:22])=[CH:20][C:5]2[C:6]3[N:10]=[C:9]([C:11]([O:13][CH2:14][CH3:15])=[O:12])[N:8]([CH3:23])[C:7]=3[CH:16]3[CH2:19][CH:18]([C:4]=2[CH:3]=1)[CH2:17]3

Participants

5

Reactant 3

HCID 6328Methyl iodideHCID 11430Potassium CarbonateHCID 86693491Ethyl 8-fluoro-9-iodo-3,4,5,6-tetrahydro-4,6-methanobenzo[3,4]cyclohepta[1,2-d]imidazole-2-carboxylate

Product 1

HCID 86693494Ethyl 8-fluoro-9-iodo-3-methyl-3,4,5,6-tetrahydro-4,6methanobenzo[3,4]cyclohepta[1,2-d]imidazole-2-carboxylateYield 94.1%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Conditions

Temperature
40 °C

Procedure

To a pressure tube containing a solution of ethyl 8-fluoro-9-iodo-3,4,5,6-tetrahydro-4,6-methanobenzo[3,4]cyclohepta[1,2-d]imidazole-2-carboxylate (400 mg at 69% purity) in N,N-dimethylformamide (0.5 mL) was introduced potassium carbonate (134 mg, 0.97 mmol) and methyl iodide (207 mg, 1.46 mol). The pressure tube was closed under an atmosphere of nitrogen and the reaction mixture warmed to 40° C. for 2.5 hr and room temperature for 12 hr. After concentrating the reaction mixture in vacuo, the residue was suspended in ethyl acetate (30 mL) and washed with saturated aqueous sodium bicarbonate (2×10 m), water (2×10 ml) and brine (10 mL). The organic extract was dried over sodium sulfate, filtered and evaporated in vacuo to furnish the crude title compound (389 mg of 77% purity LCMS-UV215) as an orange-brown sticky solid which was used for the next step without further purification. For characterisation purposes, some of the crude product was taken and suspended in ethyl acetate by sonnication and the product, an off-white solid, collected by filtration: 1H NMR (500 MHz, CDCl3) δ 1.48 (t, J=7.09 Hz, 3H), 1.69-1.74 (m, 2H), 2.92-3.00 (m, 2H), 3.50 (td, J=7.57, 3.78 Hz, 1H), 3.56 (td, J=8.35, 3.78 Hz, 1H), 3.94 (s, 3H), 4.46 (q, J=7.15 Hz, 2H), 6.79 (d, J=8.83 Hz, 1H), 8.83 (d, J=6.62 Hz, 1H); M+1=427.

Workup

  1. customThe pressure tube was closed under an atmosphere of nitrogen
  2. concentrationAfter concentrating the reaction mixture in vacuo
  3. washwashed with saturated aqueous sodium bicarbonate (2×10 m), water (2×10 ml) and brine (10 mL)
  4. extractionThe organic extract
  5. dry with materialwas dried over sodium sulfate
  6. filtrationfiltered
  7. customevaporated in vacuo

Sources & evidence

ORD record
ord-39183d83d25c472183c09eddb623660d
Source dataset
uspto-grants-2015_05
Patent number
US09034866B2

Reaction notes

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