Aluminium lithium hydride → (2-Benzyloxy-ethyl)-(2-chloro-5-methoxyphenyl)amine

HRID 1753915Notes

Reaction equation

HRID 1753915 reaction equation
[CH2:1]([O:8][CH2:9][C:10]([NH:12][C:13]1[CH:18]=[C:17]([O:19][CH3:20])[CH:16]=[CH:15][C:14]=1[Cl:21])=O)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.[H-].[Al+3].[Li+].[H-].[H-].[H-].[H][H]>C1COCC1>[CH2:1]([O:8][CH2:9][CH2:10][NH:12][C:13]1[CH:18]=[C:17]([O:19][CH3:20])[CH:16]=[CH:15][C:14]=1[Cl:21])[C:2]1[CH:3]=[CH:4][CH:5]=[CH:6][CH:7]=1

Participants

5

Reactant 3

HCID 21226445Aluminium lithium hydride2×HCID 666798212-(benzyloxy)-N-(2-chloro-5-methoxyphenyl)acetamideHCID 178418361HCID 178418361, compound

Product 1

HCID 66679111(2-Benzyloxy-ethyl)-(2-chloro-5-methoxyphenyl)amineYield 101.7%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

2-Benzyloxy-N-(2-chloro-5-methoxy-phenyl)acetamide (2) (18.9 g, 62.0 mmol) in THF (100 mL) was stirred and lithium aluminium hydride (4.9 g, 130.0 mmol) was added slowly over 15 min. There was a rapid evolution of hydrogen gas as the first of the lithium aluminium hydride was added. The reaction was then heated to reflux for 4 h and allowed to stand at RT over the weekend. The reaction was then quenched by the dropwise addition of water (50 mL) to the stirred solution. There was a violent evolution of hydrogen causing the reaction mixture to reflux. The reaction was then concentrated in vacuum to a slurry. Water (200 mL) and ethyl acetate (200 mL) were added and the mixture vigorously shaken. The reaction was then filtered through celite to remove the precipitated aluminium hydroxide and the ethyl acetate solution was separated, dried over magnesium sulfate and concentrated in vacuo to afford 18.4 g (quantitative) of (2-Benzyloxy-ethyl)-(2-chloro-5-methoxyphenyl)amine (3) as a gum. The structure was confirmed by 13C NMR (75 MHz, CDCl3) δC 43.3, 55.3, 68.2, 73.0, 98.1, 101.8, 111.6, 127.6, 127.7, 128.4, 129.3, 137.9, 144.8, and 159.5.

Workup

  1. additionwas added
  2. temperatureThe reaction was then heated
  3. temperatureto reflux for 4 h
  4. customto stand at RT over the weekend
  5. customThe reaction was then quenched by the dropwise addition of water (50 mL) to the stirred solution
  6. temperatureto reflux
  7. concentrationThe reaction was then concentrated in vacuum to a slurry
  8. additionWater (200 mL) and ethyl acetate (200 mL) were added
  9. filtrationThe reaction was then filtered through celite
  10. customto remove the precipitated aluminium hydroxide
  11. customthe ethyl acetate solution was separated
  12. dry with materialdried over magnesium sulfate
  13. concentrationconcentrated in vacuo

Sources & evidence

ORD record
ord-29104e9995d347cdb38fd2a2e361c7c0
Source dataset
uspto-grants-2015_10
Patent number
US09168317B2

Reaction notes

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