Methyl iodide → 3-[4-(3-{[tert-Butyl(dimethyl)silyl]oxy}propyl)phenyl]-2-cyano-N-cyclopropyl-N-(2,3-dichlorobenzyl)-2-methylpropanamide

HRID 561849Notes

Reaction equation

HRID 561849 reaction equation
[Si:1]([O:8][CH2:9][CH2:10][CH2:11][C:12]1[CH:17]=[CH:16][C:15]([CH2:18][CH:19]([C:35]#[N:36])[C:20]([N:22]([CH:32]2[CH2:34][CH2:33]2)[CH2:23][C:24]2[CH:29]=[CH:28][CH:27]=[C:26]([Cl:30])[C:25]=2[Cl:31])=[O:21])=[CH:14][CH:13]=1)([C:4]([CH3:7])([CH3:6])[CH3:5])([CH3:3])[CH3:2].[CH3:37][Si]([N-][Si](C)(C)C)(C)C.[K+].IC>C1COCC1>[Si:1]([O:8][CH2:9][CH2:10][CH2:11][C:12]1[CH:17]=[CH:16][C:15]([CH2:18][C:19]([C:35]#[N:36])([CH3:37])[C:20]([N:22]([CH:32]2[CH2:34][CH2:33]2)[CH2:23][C:24]2[CH:29]=[CH:28][CH:27]=[C:26]([Cl:30])[C:25]=2[Cl:31])=[O:21])=[CH:14][CH:13]=1)([C:4]([CH3:7])([CH3:6])[CH3:5])([CH3:3])[CH3:2]

Participants

5

Reactant 3

HCID 6328Methyl iodideHCID 3251421Potassium bis(trimethylsilyl)amideHCID 667617693-[4-(3-{[tert-Butyl(dimethyl)silyl]oxy}propyl)phenyl]-2-cyano-N-cyclopropyl-N-(2,3-dichlorobenzyl)propanamide

Product 1

HCID 667608183-[4-(3-{[tert-Butyl(dimethyl)silyl]oxy}propyl)phenyl]-2-cyano-N-cyclopropyl-N-(2,3-dichlorobenzyl)-2-methylpropanamide

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Conditions

Temperature
-40 °C

Procedure

To a solution of 3-[4-(3-{[tert-butyl(dimethyl)silyl]oxy}propyl)phenyl]-2-cyano-N-cyclopropyl-N-(2,3-dichlorobenzyl)propanamide (prepared as detailed in Example 14, 1 eq.) in THF (0.1 M) was added, at −78° C., potassium bis(trimethylsilyl)amide (15% w/w toluene solution, 1 eq.). The resulting yellow suspension was stirred at −78° C. for 15 min and at −40° C. for 15 min. Iodomethane (1 eq.) was then added and the reaction mixture was slowly warmed to RT over 14 h. The reaction was quenched with sat. aq. NH4Cl and extracted with ether. The combined organic extracts were washed with H2O and brine, dried over MgSO4 and filtered. Concentration of the filtrate in vacuo afforded a pale yellow oil. Purification of the crude product thus obtained by way of column chromatography (SiO2, 10:1→1:1 (v/v) Hex:EtOAc) afforded the title compound as a colorless oil.

Workup

  1. temperaturethe reaction mixture was slowly warmed to RT over 14 h
  2. customThe reaction was quenched with sat. aq. NH4Cl
  3. extractionextracted with ether
  4. washThe combined organic extracts were washed with H2O and brine
  5. dry with materialdried over MgSO4
  6. filtrationfiltered
  7. customConcentration of the filtrate in vacuo afforded a pale yellow oil
  8. customPurification of the crude product
  9. customthus obtained by way of column chromatography (SiO2, 10:1→1:1 (v/v) Hex:EtOAc)

Sources & evidence

ORD record
ord-bb00b46c0cf64941be0c42daf6d5f6d4
Source dataset
uspto-grants-2011_11
Patent number
US08063105B2

Reaction notes

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