Methyl iodide → HCID 67412422, compound

HRID 909170Notes

Reaction equation

HRID 909170 reaction equation
[C:1]([O:5][C:6](=[O:27])[NH:7][CH2:8][C:9]1[CH:14]=[C:13]([F:15])[CH:12]=[CH:11][C:10]=1[O:16][C:17]1[CH:18]=[C:19]2[C:23](=[CH:24][CH:25]=1)[N:22]([CH3:26])[N:21]=[CH:20]2)([CH3:4])([CH3:3])[CH3:2].[H-].[Na+].[CH3:30]I.[NH4+].[Cl-]>CN(C=O)C>[C:1]([O:5][C:6](=[O:27])[N:7]([CH2:8][C:9]1[CH:14]=[C:13]([F:15])[CH:12]=[CH:11][C:10]=1[O:16][C:17]1[CH:18]=[C:19]2[C:23](=[CH:24][CH:25]=1)[N:22]([CH3:26])[N:21]=[CH:20]2)[CH3:30])([CH3:4])([CH3:3])[CH3:2]

Participants

6

Reactant 4

HCID 6328Methyl iodideHCID 24758Sodium hydrideHCID 25517Ammonium ChlorideHCID 67411405HCID 67411405, compound

Product 1

HCID 67412422HCID 67412422, compoundYield 99.9%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Conditions

Temperature
0 °C

Procedure

Intermediate (26t) (50 mg, 0.135 mmol) was dissolved in DMF (2 mL) and cooled to 0° C. Sodium hydride (60%, 8.1 mg, 0.20 mmol) and methyl iodide (42 μL, 95.5 mg, 0.67 mmol) were added to the solution at 0° C. and then the mixture was allowed to warm to room temperature. After 1 hour of stirring, the mixture was poured into saturated NH4Cl solution and extracted 3 times with 30 mL of ether. The combined organic layer was washed with 5 mL of water twice and brine one, dried over MgSO4 and evaporated under reduced pressure. The pale yellow residue was purified on silica gel with EtOAc/hexane (1:2) to obtain compound (27t) as a colorless oil (52 mg, quantitative). 1HNMR (400 MHz, CDCl3) δ 7.83 (s, 1H), 7.35 (s, 0.4H), 7.33 (s, 0.6H), 7.11 (s, 0.6H), 7.08 (s, 1.4H), 6.98 (d, J=8.6 Hz, 1H), 6.92-6.81 (m, 1), 6.81-6.73 (m, 1H), 4.49 (s, 0.8H), 4.45 (s, 1.2H), 4.04 (s, 3H), 2.89 (s, 1.8H), 2.85 (s, 1.2H), 1.45 (s, 3.6H), 1.41 (s, 5.4H) ppm.

Workup

  1. temperatureto warm to room temperature
  2. extractionextracted 3 times with 30 mL of ether
  3. washThe combined organic layer was washed with 5 mL of water twice
  4. dry with materialbrine one, dried over MgSO4
  5. customevaporated under reduced pressure
  6. customThe pale yellow residue was purified on silica gel with EtOAc/hexane (1:2)

Sources & evidence

ORD record
ord-d7ba73da7b0b4e8e8f3e4814bcc36473
Source dataset
uspto-grants-2011_09
Patent number
US08017641B2

Reaction notes

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