Methyl iodide → HCID 14375144, compound

HRID 1174405Notes

Reaction equation

HRID 1174405 reaction equation
C[Si]([N-][Si](C)(C)C)(C)C.[K+].[C:11]1([C:17]2([NH:30][C@H:31]([C:37]([O:39][C:40]([CH3:43])([CH3:42])[CH3:41])=[O:38])[CH2:32][C:33]([O:35][CH3:36])=[O:34])[C:29]3[CH:28]=[CH:27][CH:26]=[CH:25][C:24]=3[C:23]3[C:18]2=[CH:19][CH:20]=[CH:21][CH:22]=3)[CH:16]=[CH:15][CH:14]=[CH:13][CH:12]=1.[CH3:44]I.[NH4+].[Cl-]>C1(C)C=CC=CC=1.O1CCCC1.O>[CH3:44][CH:32]([C:33]([O:35][CH3:36])=[O:34])[C@@H:31]([C:37]([O:39][C:40]([CH3:43])([CH3:42])[CH3:41])=[O:38])[NH:30][C:17]1([C:11]2[CH:16]=[CH:15][CH:14]=[CH:13][CH:12]=2)[C:29]2[CH:28]=[CH:27][CH:26]=[CH:25][C:24]=2[C:23]2[C:18]1=[CH:19][CH:20]=[CH:21][CH:22]=2

Participants

8

Reactant 4

HCID 6328Methyl iodide2×HCID 25517Ammonium ChlorideHCID 3251421Potassium bis(trimethylsilyl)amide2×HCID 10863156HCID 10863156, compound

Product 1

HCID 14375144HCID 14375144, compoundYield 26.2%

Reagents, catalysts & solvents 3

HCID 962WaterSolventHCID 1140TolueneSolvent2×HCID 8028TetrahydrofuranSolvent2×

Conditions

Temperature
-78 °C

Procedure

Potassium bis(trimethylsilyl)amide in toluene (1.6 mL, 0.5M) was added to tetrahydrofuran (3 mL) and cooled to −78° C. A solution of Example 183B (300 mg, 0.66 mmol) in tetrahydrofuran (2 mL) was added dropwise and stirring was continued at −78° C. for 20 minutes. Methyl iodide (102 uL, 1.64 mmol) was added and the solution was stirred at −78° C. for 3 hours. Potassium bis(trimethylsilyl)amide in toluene (1.6 mL, 0.5M) was added and the solution stirred for another 20 minutes at −78° C. Methyl iodide (102 uL, 1.64 mmol) was added and the solution was warmed to ambient temperature and stirred for 72 hours. To this solution was added 10 mL of saturated NH4Cl and 10 mL of H2O. The resulting solution was extracted with ethyl acetate (3 times 20 mL), the organic extracts were combined, washed with saturated brine solution (20 mL) and dried (Na2SO4). The solution was filtered and the filtrate concentrated to yield a crude residue which was purified by column chromatography on silica gel (3% ethyl acetate/hexane) to give the title compound (79 mg, 25%).

Workup

  1. stirringthe solution was stirred at −78° C. for 3 hours
  2. stirringthe solution stirred for another 20 minutes at −78° C
  3. temperaturethe solution was warmed to ambient temperature
  4. stirringstirred for 72 hours
  5. extractionThe resulting solution was extracted with ethyl acetate (3 times 20 mL)
  6. washwashed with saturated brine solution (20 mL)
  7. dry with materialdried (Na2SO4)
  8. filtrationThe solution was filtered
  9. concentrationthe filtrate concentrated
  10. customto yield a crude residue which
  11. customwas purified by column chromatography on silica gel (3% ethyl acetate/hexane)

Sources & evidence

ORD record
ord-5f0c30d692204ea091af44aba182f45b
Source dataset
uspto-grants-2010_11
Patent number
US07834043B2

Reaction notes

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