N,N,N',N'-Tetramethylethylenediamine → HCID 13822798, compound

HRID 1761717Notes

Reaction equation

HRID 1761717 reaction equation
[CH3:1][Si:2]([CH3:9])([CH3:8])[NH:3][Si:4]([CH3:7])([CH3:6])[CH3:5].C([Li:14])CCC.CCCCCC.Br[C:22]1[N:36]([Si](C(C)(C)C)(C)C)[C:35]2[C:44]3[C:23]=1[CH2:24][C@@H:25]1[C@@H:30]([C:31]=3[CH:32]=[CH:33][CH:34]=2)[CH2:29][C@H:28]([NH:45][C:46](=[O:52])[N:47]([CH2:50][CH3:51])[CH2:48][CH3:49])[CH2:27][N:26]1[CH3:53].CN(C)CCN(C)C.C([Li])(C)(C)C.[C:67]1([S:73]SC2C=CC=CC=2)[CH:72]=[CH:71][CH:70]=[CH:69][CH:68]=1>C1(C)C=CC=CC=1.O>[CH3:1][Si:2]([N-:3][Si:4]([CH3:7])([CH3:6])[CH3:5])([CH3:9])[CH3:8].[Li+:14].[CH2:48]([N:47]([CH2:50][CH3:51])[C:46]([NH:45][C@H:28]1[CH2:29][C@H:30]2[C@@H:25]([CH2:24][C:23]3[C:44]4[C:35](=[CH:34][CH:33]=[CH:32][C:31]2=4)[NH:36][C:22]=3[S:73][C:67]2[CH:72]=[CH:71][CH:70]=[CH:69][CH:68]=2)[N:26]([CH3:53])[CH2:27]1)=[O:52])[CH3:49]

Participants

11

Reactant 7

HCID 8037N,N,N',N'-TetramethylethylenediamineHCID 8058HexaneHCID 13436Diphenyl disulfideHCID 13838HexamethyldisilazaneHCID 13822794HCID 13822794, compoundHCID 178418306HCID 178418306, compoundHCID 178418339Butyllithium

Product 2

HCID 2733832Lithium HexamethyldisilazideHCID 13822798HCID 13822798, compoundYield 51%

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 1140TolueneSolvent3×

Conditions

Temperature
-90 °C

Procedure

At 0° C., a solution of lithium bis(trimethylsilyl)amide is prepared from 4 ml of anhydrous toluene, 0.32 ml of anhydrous, freshly distilled hexamethyldisilazane (1.5 mmol) and 0.85 ml of n-butyllithium in hexane (1.4 mmol). A solution of 533 mg of 3-[2-bromo-1-(tert-butyldimethylsilyl)-6-methyl-8α-ergolinyl]-1,1-diethylurea (1 mmol) in 50 ml of anhydrous, freshly distilled toluene is added to this solution, and the mixture is stirred for another 15 minutes. After adding 0.8 ml of distilled tetramethylethylenediamine, the mixture is cooled to -90° C., combined with 4.5 ml of tert-butyllithium (6.3 mmol), further stirred for two minutes, and the thus-formed 2-lithium compound is made to react with 2.2 g of diphenyldisulfide (10 mmol), dissolved in 10 ml of anhydrous, freshly distilled toluene, at -70° C. After 30 minutes of agitation at -70° C., water is added, the toluene phase is separated, and the aqueous phase is extracted by shaking with methylene chloride. The organic phases are dried with sodium sulfate and evaporated, the residue is chromatographed on silica gel. The yield is 523 mg of 3-[1-(tertbutyldimethylsilyl)-6-methyl-2-phenylthio-8α-ergolinyl]-1,1-diethylurea (70% of theory). This compound is dissolved in 10 ml of methanol and stirred with 1 ml of 14N potassium hydroxide solution at room temperature for 20 hours. Water is added to this mixture, the latter is stirred in an ice bath for 30 minutes, and the precipitate is suctioned off, yielding 344 mg (82% of theory). Recrystallization from methanol yields 229 mg of the final product (total yield 51%),

Workup

  1. stirringfurther stirred for two minutes
  2. customat -70° C
  3. waitAfter 30 minutes of agitation at -70° C.
  4. customthe toluene phase is separated
  5. extractionthe aqueous phase is extracted
  6. stirringby shaking with methylene chloride
  7. dry with materialThe organic phases are dried with sodium sulfate
  8. customevaporated
  9. customthe residue is chromatographed on silica gel
  10. dissolutionThis compound is dissolved in 10 ml of methanol
  11. stirringstirred with 1 ml of 14N potassium hydroxide solution at room temperature for 20 hours
  12. additionWater is added to this mixture
  13. stirringthe latter is stirred in an ice bath for 30 minutes
  14. customyielding 344 mg (82% of theory)
  15. customRecrystallization from methanol

Sources & evidence

ORD record
ord-4751929795864986ac12db387ef18294
Source dataset
uspto-grants-1989_05
Patent number
US04826851

Reaction notes

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