Aluminium lithium hydride → 2-(4-Benzyloxy-5-fluoro-1H-indol-3-yl)-N,N-dimethylethanamine

HRID 1404075Notes

Reaction equation

HRID 1404075 reaction equation
[CH2:1]([O:8][C:9]1[C:17]([F:18])=[CH:16][CH:15]=[C:14]2[C:10]=1[C:11]([C:19](=O)[C:20]([N:22]([CH3:24])[CH3:23])=O)=[CH:12][NH:13]2)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.[H-].[H-].[H-].[H-].[Li+].[Al+3]>O1CCOCC1>[CH2:1]([O:8][C:9]1[C:17]([F:18])=[CH:16][CH:15]=[C:14]2[C:10]=1[C:11]([CH2:19][CH2:20][N:22]([CH3:23])[CH3:24])=[CH:12][NH:13]2)[C:2]1[CH:3]=[CH:4][CH:5]=[CH:6][CH:7]=1

Participants

4

Reactant 2

HCID 21226445Aluminium lithium hydrideHCID 669271792-(4-Benzyloxy-5-fluoro-1H-indol-3-yl)-N,N-dimethyl-2-oxoacetamide

Product 1

HCID 669270882-(4-Benzyloxy-5-fluoro-1H-indol-3-yl)-N,N-dimethylethanamineYield 80%

Reagents, catalysts & solvents 1

HCID 312751,4-DioxaneSolvent2×

Procedure

A solution of 1-6a (2.26 g, 6.647 mmol) in dry 1,4-dioxane (30 mL) was added dropwise to a slurry of LiAlH4 (2.52 g, 66.47 mmol) in dry 1,4-dioxane (40 mL) at reflux. The mixture was held at reflux for 1 h. The mixture was then cooled, quenched with ice-water (mixed with NaOH), filtered through Celite, and the filter cake was washed with EtOAc. The filtrate and EtOAc washings were combined and extracted three times with EtOAc. The organic layer was washed with 1 N NaOH and brine, dried over Na2SO4 and concentrated. The resulting residue was purified by column chromatography on silica gel with CH2Cl2 (100%) to 5% NH4OH in CH2Cl2 as eluent to give the product (1-7a) as a brown oil in 80% yield, 1.67 g. 1H NMR (300 MHz, CDCl3-d) δ (ppm) 2.14 (s, 6H). 2.52-2.57 (m, 2H), 2.91-2.97 (m, 2H), 5.25 (s, 2H), 6.92-6.98 (m, 3H), 7.31-7.40 (m, 3H), 7.49-7.52 (m, 2H), 7.97 (br, 1H). APCI [M+1]: 313.1.

Workup

  1. temperatureat reflux
  2. temperatureat reflux for 1 h
  3. temperatureThe mixture was then cooled
  4. customquenched with ice-water (mixed with NaOH)
  5. filtrationfiltered through Celite
  6. washthe filter cake was washed with EtOAc
  7. extractionextracted three times with EtOAc
  8. washThe organic layer was washed with 1 N NaOH and brine
  9. dry with materialdried over Na2SO4
  10. concentrationconcentrated
  11. customThe resulting residue was purified by column chromatography on silica gel with CH2Cl2 (100%) to 5% NH4OH in CH2Cl2 as eluent

Sources & evidence

ORD record
ord-7a972c7ab89242f9ba4b813a54828a83
Source dataset
uspto-grants-2014_12
Patent number
US08912220B2

Reaction notes

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