Bromoacetonitrile → HCID 57446165, compound

HRID 1172394Notes

Reaction equation

HRID 1172394 reaction equation
[CH2:1]([O:3][C:4](=[O:15])[C:5]([C:12](=[O:14])[CH3:13])([CH3:11])[CH2:6][CH:7]=[C:8]([CH3:10])[CH3:9])[CH3:2].C[Si]([N-][Si](C)(C)C)(C)C.[Li+].Br[CH2:27][C:28]#[N:29].[O-2].[Al+3].[O-2].[O-2].[Al+3]>O1CCCC1>[CH2:1]([O:3][C:4](=[O:15])[C:5]([C:12](=[O:14])[CH2:13][CH2:27][C:28]#[N:29])([CH3:11])[CH2:6][CH:7]=[C:8]([CH3:9])[CH3:10])[CH3:2]

Participants

6

Reactant 4

HCID 11534BromoacetonitrileHCID 539291HCID 539291, compoundHCID 2733832Lithium HexamethyldisilazideHCID 9989226Alumina

Product 1

HCID 57446165HCID 57446165, compoundYield 71%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent2×

Conditions

Temperature
-78 °C

Procedure

A solution of 2-acetyl-2,5-dimethyl-hex-4-enoic acid ethyl ester (1.0 g, 4.71 mmol) in anhydrous tetrahydro furan (30 mL) was treated with a 1.0 M solution of lithium bis(trimethylsilyl)amide in tetrahydrofuran (5.2 mL, 5.18 mmol) at −78° C. The reaction mixture was stirred at −78° C. for 30 min and was then added via cannula to a solution of bromoacetonitrile (which was stirred for 30 min over basic aluminum oxide, filtered and used fresh in the reaction) in anhydrous tetrahydrofuran (5 mL) cooled to −78° C. The reaction mixture was stirred at −78° C. for 1 h, before it was allowed to warm to 25° C. and quenched by pouring it over ice in a 1.0 M aqueous hydrochloric acid solution. The mixture was extracted with ethyl acetate (3×100 mL), dried over magnesium sulfate, filtered and concentrated in vacuo. Further purification by flash column chromatography (ISCO RediSep column, 0 to 40% ethyl acetate in hexanes) afforded the desired product, 2-(3-cyano-propionyl)-2,5-dimethyl-hex-4-enoic acid ethyl ester (0.71 g, 71%), as an oil. 1H NMR (400 MHz, CDCl3) δ: 1.28 (3H, t, J=7.0 Hz), 1.36 (3H, s), 1.63 (3H, s), 1.70 (3H, s), 2.52-2.62 (4H, m), 2.76-2.91 (2H, m), 4.20 (2H, q, J=7.0 Hz), 4.91-4.95 (1H, m). LC-MS (ESI) calcd for C14H21NO3: 251.15, found 252.3 [M+H+].

Workup

  1. filtrationfiltered
  2. customused fresh in the reaction) in anhydrous tetrahydrofuran (5 mL)
  3. temperaturecooled to −78° C
  4. stirringThe reaction mixture was stirred at −78° C. for 1 h, before it
  5. temperatureto warm to 25° C.
  6. customquenched
  7. additionby pouring it over ice in a 1.0 M aqueous hydrochloric acid solution
  8. extractionThe mixture was extracted with ethyl acetate (3×100 mL)
  9. dry with materialdried over magnesium sulfate
  10. filtrationfiltered
  11. concentrationconcentrated in vacuo
  12. customFurther purification by flash column chromatography (ISCO RediSep column, 0 to 40% ethyl acetate in hexanes)

Sources & evidence

ORD record
ord-cbb0476096d046ce8c3d1acc5d72a391
Source dataset
uspto-grants-2010_11
Patent number
US07834009B2

Reaction notes

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