N,N,N',N'-Tetramethylethylenediamine → HCID 178503127, compound

HRID 1249551Notes

Reaction equation

HRID 1249551 reaction equation
[CH3:1][CH:2]([C:4]1[N:5]=[CH:6][N:7](C(OCC)C)[C:8]=1[C:9]1[CH:14]=[CH:13][C:12]([S:15][CH3:16])=[CH:11][CH:10]=1)[CH3:3].CN(C)CCN(C)C.C([Li])CCC.[F:35][C:36]([F:44])([F:43])[C:37]([C:39]([F:42])([F:41])[F:40])=[O:38].C(=O)(O)[O-].[Na+]>O1CCCC1.CCCCCC>[CH3:3][CH:2]([C:4]1[N:5]=[C:6]([C:37]([C:39]([F:42])([F:41])[F:40])([C:36]([F:44])([F:43])[F:35])[OH:38])[NH:7][C:8]=1[C:9]1[CH:10]=[CH:11][C:12]([S:15][CH3:16])=[CH:13][CH:14]=1)[CH3:1]

Participants

8

Reactant 5

HCID 8037N,N,N',N'-TetramethylethylenediamineHCID 12695HexafluoroacetoneHCID 516892Sodium BicarbonateHCID 137544744-(1-Methylethyl)-5-(4-methylthiophenyl)-1-(alpha-ethoxyethyl)imidazoleHCID 178418339Butyllithium

Product 1

HCID 178503127HCID 178503127, compoundYield 59%

Reagents, catalysts & solvents 2

HCID 8028TetrahydrofuranSolventHCID 8058HexaneSolvent

Conditions

Temperature
-78 °C

Procedure

To a stirred solution of 4-(1-methyethyl)-5-(4-methylthiophenyl)-1-(α-ethoxyethyl)imidazole (9.8 g, 32.2 mmol) in 110 ml of dry tetrahydrofuran was added 4.31 g (37.1 mmoles) of tetramethylethylenediamine. The reaction mixture was cooled to -78° C. and 32.24 ml of 1.65M n-butyl lithium in hexane was added dropwise via an addition funnel. After stirring the mixture an additional 20 minutes, hexafluoroacetone (9.0 ml) was condensed and added dropwise. The mixture was stirred at -78° C. for 1 hour and then 150 ml of saturated aqueous sodium bicarbonate solution was added dropwise. The reaction mixture was warmed to room temperature and the organic layer was separated. The aqueous layer was extracted with ethyl acetate. The organic layers were combined and concentrated to dryness in vacuo. The residue was stirred overnight in 215 ml of ethanol and 215 ml of 2N aqueous hydrochloric acid. The ethanol was removed in vacuo and the reaction mixture was basified to a pH of 8 with saturated aqueous potassium carbonate. The reaction mixture was extracted with ether, washed with 10% aqueous sodium bicarbonate and dried over anhydrous potassium carbonate. The residue was purified via flash chromatography on silica gel (92:8 hexane/ethyl acetate) to afford 7.55 g (59%) of a yellow oil which was triturated with hexane to give 7.55 g (59%) of the product as a white crystalline solid, m.p. 115°-117° C.

Workup

  1. customcondensed
  2. additionadded dropwise
  3. temperatureThe reaction mixture was warmed to room temperature
  4. customthe organic layer was separated
  5. extractionThe aqueous layer was extracted with ethyl acetate
  6. concentrationconcentrated to dryness in vacuo
  7. stirringThe residue was stirred overnight in 215 ml of ethanol
  8. customThe ethanol was removed in vacuo
  9. extractionThe reaction mixture was extracted with ether
  10. washwashed with 10% aqueous sodium bicarbonate
  11. dry with materialdried over anhydrous potassium carbonate
  12. customThe residue was purified via flash chromatography on silica gel (92:8 hexane/ethyl acetate)

Sources & evidence

ORD record
ord-b28df52bf88447249a82ac985a081cc5
Source dataset
uspto-grants-1986_12
Patent number
US04632930

Reaction notes

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