Methyl iodide → Lithium Hexamethyldisilazide

HRID 1838799Notes

Reaction equation

HRID 1838799 reaction equation
[Li:1]CCCC.CCCCCC.[CH3:12][Si:13]([NH:16][Si:17]([CH3:20])([CH3:19])[CH3:18])([CH3:15])[CH3:14].CI.[NH4+].[Cl-]>C1COCC1.CN1C(=O)N(C)CCC1>[CH3:12][Si:13]([CH3:15])([CH3:14])[N-:16][Si:17]([CH3:20])([CH3:19])[CH3:18].[Li+:1]

Participants

7

Reactant 4

HCID 6328Methyl iodideHCID 13838HexamethyldisilazaneHCID 25517Ammonium ChlorideHCID 178418244HCID 178418244, compound

Product 1

HCID 2733832Lithium Hexamethyldisilazide

Reagents, catalysts & solvents 2

HCID 8028TetrahydrofuranSolvent2×HCID 816462(1H)-Pyrimidinone, tetrahydro-1,3-dimethyl-Solvent

Procedure

Lithium hexamethyldisilazide was prepared by addition of 1.24 ml of 1.55 M BuLi-hexane solution at −40° C. to a solution of 0.44 ml of bistrimethylsilylamine in 4 ml of THF. After stirring for ½ h a solution of 0.56 g of 59 and 0.46 ml of DMPU in 8 ml of THF was added. Stirring was continued for 45 min at −40° C. followed by addition of 140 μl of methyliodide. Upon stirring for an additional 30 min the alkylation was complete. The mixture was poured into 40 ml of sat NH4Cl solution and extracted with ethyl acetate. Chromatographic purification provided 0.55 g of 16α-methylated product 60. Rf 0.73 (hept/ethyl ac. 1/1)starting material Rf 0.69; NMR δ 1.11 (d, 3, 16αCH3), 1.02 (s, 3, 18CH3), 0.82 (d, 3, 7αCH3), 0.91 (d, 3, 11βCH3).

Workup

  1. additionwas added
  2. stirringUpon stirring for an additional 30 min the alkylation
  3. extractionextracted with ethyl acetate
  4. customChromatographic purification

Sources & evidence

ORD record
ord-1ba9901b39674dfe8ef9c84ca19ceb5d
Source dataset
uspto-grants-2004_01
Patent number
US06677329B1

Reaction notes

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