Methyl iodide → HCID 86694685, compound

HRID 475080Notes

Reaction equation

HRID 475080 reaction equation
[H-].[Na+].[CH3:3][C:4]1[N:5]([C:10]2[CH:14]=[C:13]([C:15]3([OH:19])[CH2:18][O:17][CH2:16]3)[N:12]([CH2:20][O:21][CH2:22][CH2:23][Si:24]([CH3:27])([CH3:26])[CH3:25])[N:11]=2)[C:6]([CH3:9])=[CH:7][CH:8]=1.[C:28](=[S:30])=[S:29].I[CH3:32]>C1COCC1>[CH3:3][C:4]1[N:5]([C:10]2[CH:14]=[C:13]([C:15]3([O:19][C:28]([S:30][CH3:32])=[S:29])[CH2:16][O:17][CH2:18]3)[N:12]([CH2:20][O:21][CH2:22][CH2:23][Si:24]([CH3:25])([CH3:27])[CH3:26])[N:11]=2)[C:6]([CH3:9])=[CH:7][CH:8]=1

Participants

6

Reactant 4

HCID 6328Methyl iodideHCID 6348Carbon DisulfideHCID 24758Sodium hydrideHCID 71272554HCID 71272554, compound

Product 1

HCID 86694685HCID 86694685, compoundYield 101.7%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent4×

Conditions

Temperature
0 °C

Procedure

Into a 2 L 3-necked round-bottom flask under nitrogen was placed THF (800 mL), followed by the addition of NaH (10.4 g, 260 mmol, 1.50 equiv., 60% suspension) in several batches at 0° C. over 10 min. To this suspension was added a solution of 3-[3-(2,5-dimethyl-1H-pyrrol-1-yl)-1-[[2-(trimethylsilyl)ethoxy]methyl]-1H-pyrazol-5-yl]oxetan-3-ol (63.0 g, 173.3 mmol, 1.0 equiv.) in THF (300 mL), dropwise with stirring at 0° C. over 30 min. The resulting solution was stirred at 0° C. for 30 min. To the mixture was added a solution of CS2 (19.7 g, 259.21 mmol, 1.50 equiv.) in THF (100 mL), dropwise with stirring at 0° C. over 20 min. The resulting solution was stirred at 0° C. for 1 h. To the mixture was added a solution of iodomethane (37.0 g, 260.7 mmol, 1.5 equiv.) in THF (100 mL), dropwise with stirring at 0° C. over 10 min. The resulting solution was stirred at 0° C. for 1 h, then quenched by the addition of 300 mL of satd. aq. NH4Cl, concentrated in vacuo, diluted with 1 L of water and extracted with 3×1 L of EtOAc. The combined organic layers were washed with 2×1 L of water and 2×500 mL of brine, dried (Na2SO4) and concentrated in vacuo to afford ([3-[3-(2,5-dimethyl-1H-pyrrol-1-yl)-1-[[2-(trimethylsilyl)ethoxy]-methyl]-1H-pyrazol-5-yl]oxetan-3-yl]oxy)(methylsulfanyl)methanethione (80.0 g, 97% yield) as a yellow oil.

Workup

  1. customInto a 2 L 3-necked round-bottom flask under nitrogen was placed
  2. stirringThe resulting solution was stirred at 0° C. for 30 min
  3. stirringdropwise with stirring at 0° C. over 20 min
  4. stirringThe resulting solution was stirred at 0° C. for 1 h
  5. stirringdropwise with stirring at 0° C. over 10 min
  6. stirringThe resulting solution was stirred at 0° C. for 1 h
  7. customquenched by the addition of 300 mL of satd
  8. concentrationaq. NH4Cl, concentrated in vacuo
  9. additiondiluted with 1 L of water
  10. extractionextracted with 3×1 L of EtOAc
  11. washThe combined organic layers were washed with 2×1 L of water and 2×500 mL of brine
  12. dry with materialdried (Na2SO4)
  13. concentrationconcentrated in vacuo

Sources & evidence

ORD record
ord-1892eec9490242738a8701b4815f9e78
Source dataset
uspto-grants-2014_01
Patent number
US08637537B2

Reaction notes

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