Trimethylsilyl cyanide → HCID 59200425, compound

HRID 1685304Notes

Reaction equation

HRID 1685304 reaction equation
[Si]([C:5]#[N:6])(C)(C)C.[CH3:7][C:8]1[CH:13]=[CH:12][N:11]=[C:10]([C:14](=[O:18])[CH2:15][CH2:16][CH3:17])[CH:9]=1.[H-].[H-].[H-].[H-].[Li+].[Al+3]>C1COCC1.[Zn+2].[I-].[I-]>[NH2:6][CH2:5][C:14]([C:10]1[CH:9]=[C:8]([CH3:7])[CH:13]=[CH:12][N:11]=1)([OH:18])[CH2:15][CH2:16][CH3:17]

Participants

6

Reactant 3

HCID 82115Trimethylsilyl cyanideHCID 21226445Aluminium lithium hydrideHCID 21847508103028-75-7

Product 1

HCID 59200425HCID 59200425, compoundYield 74.5%

Reagents, catalysts & solvents 2

HCID 9883512zinc(II)iodideCatalystHCID 8028TetrahydrofuranSolvent2×

Procedure

TMSCN (0.3 mL, 2.28 mmol) followed by ZnI2 (51 mg, 0.16 mmol) were sequentially added to neat 1-(4-methylpyridin-2-yl)butan-1-one (372 mg, 2.28 mmol) with stirring under Ar. Reaction stirred at rt for 4 hours. THF (6 mL) was added to cyanohydrin, then this was slowly added dropwise over 10 min via cannula to LAH (140 mg, 3.6 mmol) in THF (10 mL) with stirring under Ar. Reaction warmed as addition progressed. Once addition was ended, reaction heated to reflux for 1 hour, then cooled to rt then in ice. To the cool reaction with stirring was added Na2SO4.10H2O, the reaction stirred overnight and was allowed to warm to RT as the bath warmed. The reaction was filtered, the solid washed with EtOAc; the organic phase extracted with 10% HCl (2×). The aqueous extracts were combined and washed with Et2O. Aqueous phase was basified to pH ˜12 with 5M NaOH, saturated with NaCl, then extracted with Et2O (3×). The combined extracts were dried (MgSO4), filtered and concentrated to afford 330 mg of 1-amino-2-(4-methylpyridin-2-yl)pentan-2-ol as an oil. 1H NMR (400 MHz, CDCl3) δ ppm 8.36 (d, J=5.05 Hz, 1H), 7.18 (s, 1H), 7.00 (d, J=5.81 Hz, 1H), 3.04 (d, J=12.88 Hz, 1H), 2.90 (d, J=12.88 Hz, 1H), 2.37 (s, 3H), 1.71 (m, 2H), 1.40 (m, 1H), 0.77-0.95 (m, 4H).

Workup

  1. customReaction
  2. stirringstirred at rt for 4 hours
  3. stirringwith stirring under Ar
  4. customReaction
  5. temperaturewarmed as addition
  6. additionOnce addition
  7. customreaction
  8. temperatureheated
  9. temperatureto reflux for 1 hour
  10. customTo the cool reaction
  11. stirringwith stirring
  12. stirringthe reaction stirred overnight
  13. temperatureto warm to RT as the bath
  14. temperaturewarmed
  15. filtrationThe reaction was filtered
  16. washthe solid washed with EtOAc
  17. extractionthe organic phase extracted with 10% HCl (2×)
  18. washwashed with Et2O
  19. extractionextracted with Et2O (3×)
  20. dry with materialThe combined extracts were dried (MgSO4)
  21. filtrationfiltered
  22. concentrationconcentrated

Sources & evidence

ORD record
ord-fd0b7cf587f24f4381ec9ce958ee9372
Source dataset
uspto-grants-2012_04
Patent number
US08148400B2

Reaction notes

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