Aluminium lithium hydride → (2S,6S)-4-Benzyl-2,6-dimethylmorpholine

HRID 1966327Notes

Reaction equation

HRID 1966327 reaction equation
[C:1]([N:9]1[CH2:14][C@H:13]([CH3:15])[O:12][C@@H:11]([CH3:16])[CH2:10]1)(=O)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.[H-].[H-].[H-].[H-].[Li+].[Al+3]>C1COCC1>[CH2:1]([N:9]1[CH2:10][C@H:11]([CH3:16])[O:12][C@@H:13]([CH3:15])[CH2:14]1)[C:2]1[CH:3]=[CH:4][CH:5]=[CH:6][CH:7]=1

Participants

4

Reactant 2

HCID 21226445Aluminium lithium hydride2×HCID 67088332[(2S,6S)-2,6-Dimethylmorpholin-4-yl](phenyl)methanone

Product 1

HCID 11183342(2S,6S)-4-Benzyl-2,6-dimethylmorpholine

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Conditions

Temperature
55 °C

Procedure

(2S,6S)-4-benzoyl-2,6-dimethylmorpholine (759 mg, 3.46 mmol) is dissolved in anhydrous THF (40 mL) and treated with LiAlH4 (1.0M in THF, 6.9 mL, Aldrich). The mixture is stirred with heating at 55° C. for 18 hours. An additional equivalent of LiAlH4 is added and the mixture is stirred with heating at 55° C. for an additional 6 hours. The reaction is quenched by adding water (0.4 mL) followed by 6.0M NaOH (0.4 mL) followed by water (1.2 mL). The white slurry is diluted with Et2O and filtered. The inorganic salts are washed with and additional portion of Et2O and the combined ethereal washes are dried over Na2SO4. The product is purified on a Biotage Flash 40M+ using a 15% Et2O in pentane as eluent. The product containing fractions are pooled and the solvent is removed by rotary evaporation. The product is dried under vacuum yielding a colorless oil.

Workup

  1. stirringthe mixture is stirred
  2. temperaturewith heating at 55° C. for an additional 6 hours
  3. customThe reaction is quenched
  4. additionby adding water (0.4 mL)
  5. additionThe white slurry is diluted with Et2O
  6. filtrationfiltered
  7. washThe inorganic salts are washed with and additional portion of Et2O
  8. dry with materialthe combined ethereal washes are dried over Na2SO4
  9. customThe product is purified on a Biotage Flash 40M+
  10. additionThe product containing fractions
  11. customthe solvent is removed by rotary evaporation
  12. customThe product is dried under vacuum
  13. customyielding a colorless oil

Sources & evidence

ORD record
ord-ce484b6a4a57407188b8a7f1cf62eb6c
Source dataset
uspto-grants-2013_04
Patent number
US08420646B2

Reaction notes

Loading…