Lithium Hexamethyldisilazide → HCID 59363800, compound

HRID 2189148Notes

Reaction equation

HRID 2189148 reaction equation
[CH2:1]([O:5][C:6]1[CH:11]=[CH:10][CH:9]=[CH:8][C:7]=1[C:12](=[O:14])[CH3:13])[CH:2]([CH3:4])[CH3:3].C[Si](C)(C)[N-][Si](C)(C)C.[Li+].[C:25]([C:27]1[CH:28]=[C:29]([CH:33]=[CH:34][C:35]=1[F:36])[C:30](Cl)=[O:31])#[N:26]>O1CCCC1>[F:36][C:35]1[CH:34]=[CH:33][C:29]([C:30](=[O:31])[CH2:13][C:12]([C:7]2[CH:8]=[CH:9][CH:10]=[CH:11][C:6]=2[O:5][CH2:1][CH:2]([CH3:4])[CH3:3])=[O:14])=[CH:28][C:27]=1[C:25]#[N:26]

Participants

5

Reactant 3

HCID 2733832Lithium HexamethyldisilazideHCID 2773933HCID 2773933, compoundHCID 15741847HCID 15741847, compound

Product 1

HCID 59363800HCID 59363800, compoundYield 68,338.898%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent2×

Conditions

Temperature
-78 °C

Procedure

To a solution of 1-(2-isobutoxyphenyl)ethanone (9.0 g, 0.047 mol) in tetrahydrofuran (150 mL) under N2 at −78° C. was added a 1.0 M solution of lithium hexamethyl disilazide in hexanes (100 mL, 2.2 eq) over 5 minutes. The reaction was stirred at −78° C. for 1 h. To the reaction solution was added 3-cyano-4-fluorobenzoyl chloride (8.6 g, 0.047 mmol) in tetrahydrofuran (28 mL) over 5 minutes at −78° C. The reaction mixture was then removed from the dry ice bath and allowed to stir for 1 h. The reaction was quenched with 1N HCl then partitioned between ethyl acetate and water. The layers were separated and the aqueous layer was extracted with ethyl acetate. The combined organic layers were dried over anhydrous magnesium sulfate, filtered and concentrated in vacuo. The resulting solid was triturated with acetonitrile and filtered yielding 10.9 g (90%) of 2-fluoro-5-(3-(2-isobutoxyphenyl)-3-oxopropanoyl)benzonitrile and was submitted to the next step without further purification.

Workup

  1. customThe reaction mixture was then removed from the dry ice bath
  2. stirringto stir for 1 h
  3. customThe reaction was quenched with 1N HCl
  4. customthen partitioned between ethyl acetate and water
  5. customThe layers were separated
  6. extractionthe aqueous layer was extracted with ethyl acetate
  7. dry with materialThe combined organic layers were dried over anhydrous magnesium sulfate
  8. filtrationfiltered
  9. concentrationconcentrated in vacuo
  10. customThe resulting solid was triturated with acetonitrile
  11. filtrationfiltered

Sources & evidence

ORD record
ord-c7c26d4216e24f258d342fdeedddc17f
Source dataset
uspto-grants-2012_12
Patent number
US08324231B2

Reaction notes

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