Methyl iodide → HCID 67455812, compound

HRID 227710Notes

Reaction equation

HRID 227710 reaction equation
IC.[H-].[Na+].[F:5][C:6]1[CH:11]=[CH:10][C:9]([CH:12]2[C:17]([C:18]([O:20][CH3:21])=[O:19])=[C:16]([CH3:22])[NH:15][C:14]([O:23][CH3:24])=[N:13]2)=[CH:8][CH:7]=1.[CH3:25]COC(C)=O>CN(C=O)C.O>[F:5][C:6]1[CH:11]=[CH:10][C:9]([CH:12]2[N:13]([CH3:25])[C:14]([O:23][CH3:24])=[N:15][C:16]([CH3:22])=[C:17]2[C:18]([O:20][CH3:21])=[O:19])=[CH:8][CH:7]=1

Participants

7

Reactant 4

HCID 6328Methyl iodideHCID 8857Ethyl AcetateHCID 24758Sodium hydrideHCID 10636289HCID 10636289, compound

Product 1

HCID 67455812HCID 67455812, compoundYield 41%

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 6228DimethylformamideSolvent2×

Conditions

Temperature
0 °C

Procedure

Iodomethane (0.314 mL, 5.04 mmol, 1.1 equiv) and sodium hydride (60% in mineral oil, 202 mg, 5.04 mmol, 1.1 equiv) were combined in DMF (10 mL) and cooled to 0° C. The product of Step (b) (1.275 g, 4.59 mmol, 1 equiv) was added slowly as a solution in DMF (11 mL). Following the addition, the reaction was warmed to room temperature and stirred for two hours. The reaction mixture was diluted with water and poured into EtOAc. The phases were separated and the aqueous phase was extracted with an additional portion of EtOAc. The combined organic phases were washed with water, 15% aq. Na2S2O4, and satd. NaCl, then dried over sodium sulfate. The suspension was filtered and the filtrate was concentrated en vacuo to afford a mixture of two regioisomeric products. The isomers were separated by flash chromatography (3→5% Et2O/CH2Cl2), and regiochemistry of the desired product was confirmed by NOE analysis. 550 mg (41%) of the title compound was isolated as a yellow solid. 1H NMR (400 MHz, CDCl3) 7.30-7.27 (m, 2H), 7.02-6.97 (m, 2H), 5.21 (s, 1H), 3.91 (s, 3H), 3.63 (s, 3H), 2.84 (s, 3H), 2.38 (s, 3H).

Workup

  1. additionthe addition
  2. temperaturethe reaction was warmed to room temperature
  3. customThe phases were separated
  4. extractionthe aqueous phase was extracted with an additional portion of EtOAc
  5. washThe combined organic phases were washed with water, 15% aq. Na2S2O4
  6. dry with materialNaCl, then dried over sodium sulfate
  7. filtrationThe suspension was filtered
  8. concentrationthe filtrate was concentrated en vacuo
  9. customto afford
  10. additiona mixture of two regioisomeric products
  11. customThe isomers were separated by flash chromatography (3→5% Et2O/CH2Cl2), and regiochemistry of the desired product

Sources & evidence

ORD record
ord-4342352c23f8412fbbe92af813cf9500
Source dataset
uspto-grants-2009_07
Patent number
US07560467B2

Reaction notes

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