Trimethylsilyl cyanide → HCID 59200374, compound

HRID 1685301Notes

Reaction equation

HRID 1685301 reaction equation
[Si]([C:5]#[N:6])(C)(C)C.[N:7]1[CH:12]=[CH:11][CH:10]=[CH:9][C:8]=1[C:13](=[O:17])[CH2:14][CH2:15][CH3:16].[H-].[H-].[H-].[H-].[Li+].[Al+3]>C1COCC1.[Zn+2].[I-].[I-]>[NH2:6][CH2:5][C:13]([C:8]1[CH:9]=[CH:10][CH:11]=[CH:12][N:7]=1)([OH:17])[CH2:14][CH2:15][CH3:16]

Participants

6

Reactant 3

HCID 82115Trimethylsilyl cyanideHCID 5563481-(pyridin-2-yl)butan-1-oneHCID 21226445Aluminium lithium hydride

Product 1

HCID 59200374HCID 59200374, compoundYield 50.9%

Reagents, catalysts & solvents 2

HCID 9883512zinc(II)iodideCatalystHCID 8028TetrahydrofuranSolvent2×

Procedure

TMSCN (1.10 mL, 8.25 mmol) followed by ZnI2 (163 mg, 0.51 mmol) were sequentially added to neat 1-(pyridin-2-yl)butan-1-one (1.131 g, 7.58 mmol) with stirring under Ar. The reaction was stirred at RT for 1 hour. THF (13 mL) was added to cyanohydrin, then this was slowly added dropwise over 10 min via cannula to LAH (462 mg, 12.17 mmol) in THF (30 mL) with stirring under Ar. The reaction warmed as addition progressed. Once the addition ended, the reaction was heated to reflux for 1 hour, then cooled to RT then cooled in ice. To the cooled reaction mixture was added with stirring Na2SO4.10H2O. The reaction stirred overnight and was allowed to warm to RT as the bath warmed. The reaction was filtered, solid washed with EtOAc, the organic phase extracted with 10% HCl (2×), aqueous extracts combined and washed with Et20. The aqueous phase was basified to pH ˜12 with 5M NaOH, saturated with NaCl, and then extracted with Et2O (3×). Combined extracts were dried (MgSO4), filtered and concentrated to afford 695 mg of 1-amino-2-(pyridin-2-yl)pentan-2-ol as an oil. 1H NMR showed this to be a 1:1.6 mixture of ROTMS:ROH:1H NMR for desired product: 1H NMR (400 MHz, CDCl3) δ ppm 8.53 (m, 1H), 7.64 (td, J=7.58, 1.77 Hz, 1H), 7.58 (dt, J=7.83, 1.14 Hz, 1H), 7.10 (ddd, J=7.33, 4.80, 1.26 Hz, 1H), 3.32 (d, J=13.64 Hz, 1H), 2.87 (d, J=13.64 Hz, 1H), 0.75 (m, 3H)

Workup

  1. stirringThe reaction was stirred at RT for 1 hour
  2. stirringwith stirring under Ar
  3. temperatureThe reaction warmed as addition
  4. additionOnce the addition
  5. temperaturethe reaction was heated
  6. temperatureto reflux for 1 hour
  7. temperaturethen cooled in ice
  8. customTo the cooled reaction mixture
  9. stirringThe reaction stirred overnight
  10. temperatureto warm to RT as the bath
  11. temperaturewarmed
  12. filtrationThe reaction was filtered
  13. washsolid washed with EtOAc
  14. extractionthe organic phase extracted with 10% HCl (2×), aqueous extracts
  15. washwashed with Et20
  16. extractionextracted with Et2O (3×)
  17. dry with materialCombined extracts were dried (MgSO4)
  18. filtrationfiltered
  19. concentrationconcentrated

Sources & evidence

ORD record
ord-c7bc6bd3002044ed807bff0c1669e994
Source dataset
uspto-grants-2012_04
Patent number
US08148400B2

Reaction notes

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